Comparison of Pneumonia Management Methods

Comparison of Pneumonia Management Methods INTRODUCTION 1.1 Background: Pneumonia is the inflammation and consolidation of lung tissue due to an infectious agent (Marrie TJ, 1994). Pneumonia has the highest mortality rate among infectious diseases and represents the fifth leading cause of death (Brandstetter, 1993). Pneumonia causes excess morbidity, hospitalization, and mortality, especially among the elderly, the fastest growing sector of the population.According to first- or second-listed diagnosis, approximately 1 million persons were discharged from short-stay hospitals after treatment for pneumoniain the United States in 1990, and elderly persons aged 65 years or more accounted for 52% of all pneumonia discharges (Fedson Musher, 1994). Pneumonia has the highest mortality rate among infectious diseases and represents the fifth cause of death (Brandstltter, 1993). In addition fine (2000) reported that lower respiratory tract infections affect three million persons annually and is the leading cause of death of infection in the United States. †¢ Pneumonia represented one of the 10th leading causes of hospitalization and deaths in Malaysia through 1999-2006 (Ministry of Health, Malaysia, 1999, 2000, 2001, 2002b, 2003, 2004, 2005band 2006b) Because of differences in pathogenesis and causative micro-organisms, pneumonia is often divided into: hospital acquired and community-acquired pneumonia.Community acquired pneumonia (CAP) is caused mainly by streptococcus pneumoniae. Its symptoms include coughing (with or without sputum production), change in colour of respiratory secretion, fever, and pleuritic chest pain (Fine, 2000). Nosocomial pneumonia or hospital acquired pneumonia is the second most common nosocomial infection in the United States and it causes the highest rates of morbidity and mortality. It is caused mainly by streptococcus pneumoniae and pseudomonas aeruginosa. The highest mortality rates occurred in patients with pseudomonas aeruginosa or acineobacter infection. It is characterized by fever and purulent respiratory secretion. Nosocomial pneumonia results in increase length of hospitalization and cost of treatment (Kashuba, 1999; Levison, 2003; Wilks et al., 2003). The clinical criteria for the diagnosis o f pneumonia include chest pain, cough, or auscultatory findings such as rales or evidence of pulmonary consolidation, fever or leucocytosis. In addition, there must be radiographic evidence, such as the presence of new infiltrates on chest radiograph, and laboratory evidence that supports the diagnosis. Because of differences in pathogenesis and causative micro-organisms, pneumonia is often divided in hospital acquired and community-acquired pneumonia. Pneumonia developing outside the hospital is referred to as community-acquired pneumonia (CAP). Pharmacoeconomic study Pharmacoeconomics is defined as the description and analysis of costs of drug therapy or clinical service to health care systems and society (Bootman et al., 1996). It has risen up as the discipline with the increase interst in calculating the value and costs of medicines (Sanches, 1994). Cost is defined as the value of resources consumed by the program or drug therapy of interest while a consequence is defined as the effect, outputs, or outcomes of a program. When identifying the costs associated with a product or service, all possible costs that include or related to the study are calculated (Sanchez, 1994). With the increase in financial pressure to hospitals to minimize their medical care costs, pharmacoeconomics can define costs and benefits of both expensive drug therapies and pharmacy based clinical services (Destache, 1993; Touw, 2005).Furthermore pharmacoeconomics can assist practitioners in balancing cost and quality that may result in improving patient care and cost saving to the institution (Sanches, 1994). Bootman and Harison (1997) stated that pharmacoeconomics and outcome research are very important to determine the efficient way to present a quality care at realistic rate. They suggested that pharmacoeconomics should have a remarkable authority on the delivery and financing of health care throughout the world. Different methods have been used to perform pharmacoeconomics analysis which includes: Cost-benefit analysis: Cost-benefit analysis two or more alternatives that do not have the same outcome measures. It measures all costs and benefits of a program in monetary terms (Bootman et al., 1996; Fleurence, 2003). Cost-benefit analysis could play a major role in identifying the specific costs and benefits associated with the pneumonia. Cost-effective analysis Cost-effective analysis compares alternatives that differ in safety, efficacy and outcome. Cost is measured in monetary terms, while outcome is measured in specific objectives or natural units. The outcome are expressed in terms of the cost per unit of success or effect (Bootman et al., 1996). Cost-utility analysis Cost-utility analysis compares treatment alternatives; benefits are measured in terms of quality of life, willingness to pay, and patient preference for one intervention over another, while cost is measured in monetary terms. It has some similarity to cost-effectivness with more concentration on patient view. As an example, looking for new druig therapy; benefits can built-in together with expected risks. Cost-minimization analysis Cost-minimization analysis is one of the simplest forms of pharmacoeconomics analysis. It is used when two or more alternatives are assumed to be equivalent in terms of outcomes but differ in the cost which is measured in monetary terms (Fleurence, 2003). Cost of illness analysis Cost of illness analysis is the determination of all costs of aparticular disease, which include both direct and indirect costs. Since both costs were calculated, an economic evaluation for the disease can be performed successfully. It has been used for evaluating many diseases (Bootman et al., 1996). 1.2 Study problems and rationale The management of pneumonia is very straight forward. However this is not always true for the diagnosis and selection of therapy. As there are some issues related to pneumonia that need to be addressed : The first issue pertains to the inappropriate diagnosis of the pneumonia. Some physicians do not properly identify the causative organism, I.e, whether, it is bacterial or viral. Bartlet et al (1998) found that the viral infections have been associated with at least 10% to 15 % of CAP in hospitalized adults (Bartlet et al, 1998). Secondly is the use of inappropriate medications. The prescription of inappropriate or un-indicated drug therapy such as the prescription of antibiotics for pneumonia caused by nonbacterial infection may increase the incidence of bacterial resistance (Steinman, 2003). Thirdly the adherence to guidelines improves quality of care and reduces the length of hospital stay (Marrie TJ et al, 2000). Fourthly the adherence to guidelines reduces the cost of treating pneumonia (Feagan BG, 2001). Fifthly Teaching hospitals are widely perceived to provide good outcome, and that reputation is thought to justify these institutions comparatively higher charges relative to non-teaching (general) hospitals. Despite their reputation for specialized care, teaching hospitals have traditionally relied on revenue from routine services, such as treatment of pneumonia, and the costs of specialized services and medical training. However, with managed care and competition creating pressures for cost containment, these higher costs have come into question: Do a teaching hospital provide good outcome for management of pneumonia, or do a general hospital provide comparable outcome at lower costs? 1.3 Significance of the Study This study has the following important issues: To the researchers: Several studies have compare the management of pneumonia in a university hospital versus a general hospital, but most of these studies were conducted in the USA and other parts of the world. There are no published studies in Malaysia or Asia to our knowledge. This study also provides the difference in the outcome, cost and cost-effectivness of treating pneumonia between a university hospital and a general hospital. To the practitioners: This study will provide information about the adherence to guidelines will reduce the length of hospital stay, reduce the cost of treating pneumonia and improve outcomes of treating pneumonia. To the patients: This study attempts to highlight the benefits associated with adherence to the guidelines. To the policy makers: This study will help policy makers to develop new strategies for management of pneumonia. This study will help policy makers to develop new guideline for management of pneumonia according to the microorganisms and the population in Malaysia. This study also provides the difference in the management of pneumonia between a university hospital and a general hospital. This study will provide information about how we can reduce the length of hospital stay, reduce the cost of treating pneumonia and improve outcomes of treating pneumonia. The results of this study will help in improving the management of pneumonia. It is the time to know whether a university hospital (H-USM) provide good outcome for treating pneumonia or do a general hospital (Penang-GH) provide comparable outcome at lower costs. By analyzing the cost and effectiveness of the regimens being used, the most effective therapy can be defined and the information can be offered to the policy makers to improve the deciosion making in treating pneumonia. The study will be able to help on: How we can make the drug therapy cost effective keeping effectiveness and outcome in our mind and try to suggest the best and most appropriate drug therapy which should be cost effective which help to decrease the financial burden on patients as well as Ministry Of health. This study will help to suggest how we can reduce the cost of therapy of treating pneumonia. The study will be able to provide data on: The incidence of pneumonia in (H-USM and Penang-GH). The most common organisms causing pneumonia in (H-USM and Penang-GH). The pattern of drugs used and management of pneumonia in in (H-USM and Penang-GH). The outcome of treating pneumonia in (H-USM and Penang-GH). The cost of treating pneumonia in (H-USM and Penang-GH). The cost-effectivness of treating pneumonia in (H-USM and Penang-GH). Whether a university hospital provide a good outcome for management of pneumonia, or a general hospital provide comparable quality at lower costs. 1.4 Hypothesis of the Study: H0: There is no significant difference of the management of pneumonia between a universiry hospital (H-USM) and a general hospital (Penang-GH). H1: There is a significant difference of the management of pneumonia between a universiry hospital (H-USM) and a general hospital (Penang-GH). 1.5 Aim of the study The aim of this study is to compare the management of pneumonia in a university hospital (H-USM) versus a general hospital (Pinanag-GH). 1.6 Objectives The objectives of this study are: To compare the incidence of pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the most common organisms associated with pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the drug therapy for pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the outcome of treating pneumonia (mortality rate, length of hospitalization, pneumonia related symptoms at discharge and complications of pneumonia) at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the cost of treating pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the cost-effectivness of treating pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). 1.7 Research Questions What are the difference between the organisms that is commonly associated with pneumonia at H-USM and Penang-GH? What are the difference between the antibiotics that is commonly used for the treatment of pneumonia at H-USM and Penang-GH? What are the difference between the outcome of treating pneumonia (mortality rate, length of hospitalization, pneumonia related symptoms at discharge and complications of pneumonia) at H-USM and Penang-GH? What are the difference between the cost of treating pneumonia at H-USM and Penang-GH? And how can these costs be reduced? What are the difference between the cost-effectivness of treating pneumonia at H-USM and Penang-GH? Do a university hospital (H-USM) provide good outcome for treating pneumonia or do a general hospital (Penang-GH) provide comparable outcome at lower costs? CHPTER 2 LITERATURE REVIEW 2.1 Community-acquired pneumonia 2.1.1 Introduction Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, a new infiltrate on chest x-ray or auscultatory findings such as altered breath sounds and/or localized rales in community-dwelling patients (Infectious Diseases Society of America 2000). It is a common condition that carries a high burden of mortality and morbidity, particularly in elderly populations. Although most patients recover without sequellae, CAP can take a very severe course, requiring admission to an intensive care unit (ICU) and even leading to death. According to US data, it is the most important cause of death from infectious causes and the sixth most important cause of death overall (Adams et al. 1996). Even though the mortality from pneumonia decreased rapidly in the 1940s after the introduction of antibiotic therapy, it has remained essentially unchanged since then or has even increased slightly (MMWR 1995 ). Furthermore, significant costs are associated with the diagnosis and management of CAP. Between 22% and 42% of adults with CAP are admitted to hospital, and of those, 5% to 10% need to be admitted to an ICU (British Thoracic Society 2001). In the US, it is estimated that the total cost of treating an episode of CAP in hospital is about USD $ 7500, which is approximately 20 times more than the cost of treating a patient on an outpatient basis (Lave et al. 1999). CAP also contributes significantly to antibiotic use, which is associated with well-known problems of resistance. In treating patients with CAP, the choice of antibiotic is a difficult one. Factors to be considered are the possible etiologic pathogen, the efficacy of the substance, potential side-effects, the treatment schedule and its effect on adherence to treatment as well as the particular regional resistance profile of the causative organism and the co-morbidities that might influence the range of potential pathogens (such as in cystic fibrosis) or the dosage (as in the case of renal insufficiency). It may be a primary disease occurring at random in healthy individuals or may be secondary to a predisposing factor such as chronic lung disease or diabetes mellitus. CAP represents a broad spectrum of severity, ranging from mild pneumonia that can be managed by general practitioners outside the hospital to severe pneumonia with septic shock needing treatment in intensive care unit. Depending on severity of illness, about 20% of patients with pneumonia need hospitalization and approximately 1% of all CAP patients require treatment in ICU. Elderly persons and those with underlying conditions, such as cerebro and cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and alcoholism, are at increased risk for developing lower respiratory tract infections and complicated courses of infection. 2.1.2 Definition: Community-Acquired pneumonia (CAP) is defined as inflammation and consolidation of lung tissue induced by infectious microbes such as bacteria, viruses, or parasites. When the onset of symptoms and signs of this disease is before or within 48 hours after admission, it is considered as CAP (Bartlett JG et al., 1995). 2.1.3 Epidemiology Incidence: In the industrialized world, the annual incidence of CAP in community dwelling adults is estimated at 5 to 11 cases per 1000 adult population (British Thoracic Society 2001). The incidence is known to vary markedly with age, being higher in the very young and the elderly. In one Finnish study, the annual incidence for people aged 16-59 years was 6 cases per 1000 population, for those 60 years and older it was 20 per 1000, and for people aged 75 and over, 34 per 1000 (Jokinen et al. 1993). Annual incidences of 30-50 per 1000 population have been reported for infants below 1 year of age (Marrie 2001). Seasonal variations in incidence are also significant, with a peak in the winter months (Marrie 2001). The annual incidence of CAP requiring hospitalisation has been estimated at 1 to 4 patients per 1000 population (Marrie 1990, Fine et al. 1996). The proportion of patients requiring hospitalisation varies from country to country and across studies and has been estimated as ranging anywhe re between 15% and 56% (Foy et al. 1973, Minogue et al. 1998). Of those, 5% to 10% required admission to an intensive care unit (ICU) (British Thoracic Society Research Committee and Public Health Laboratory Service 1992, Torres et al. 1991). Conversely, about 8% to 10% of admissions to a medical ICU are due to severe CAP (Woodhead et al. 1985). Community acquired pneumonia (CAP) is a leading infectious disease cause of death throughout the world (WHO Statistical Information System (WHOSIS). WHO Mortality Database. Released: January 2005; Health, United States, 2005; Annual Report, Hong Kong, 2003/2004). Adult community-acquired pneumonia is a serious, life-threatening illness that affects more than 3 million people each year and accounts for more than half a million annual hospital admissions in the United States alone (Lynch JP, 1992). Each year, more than 900 000 cases of pneumonia occur in the United States, accounting for nearly 3% of all hospital admissions,(National Hospital Discharge Survey, 1988) and about 50 000 people die as a result of community-acquired pneumonia (Farr BM et al 203). Bartlet et al (1998) found that viral infections have been associated with at least 10% to 15 % of CAP in hospitalized adults. Adult community-acquired pneumonia is a serious, life-threatening illness that affects more than 3 million people each year and accounts for more than half a million annual hospital admissions in the United States alone. Each year, more than 900 000 cases of pneumonia occur in the United States, accounting for nearly 3% of all hospital admissions, and about 50 000 people die as a result of community-acquired pneumonia. In the USA, community acquired pneumonia is the fifth leading cause of death in people over the age of 65 years and an estimated 60 000 seniors die annually. Most of the excess deaths and hospitalizations due to lower respiratory infections occur in older adults, as reflected by the more than 44 000 hospitalizations for pneumonia and influenza in people aged 65 and older in 1997 in Canada. It is estimated that the age-specific incidence of pneumonia increases from 15.4 cases per 1000 in those aged 60-74 years to 34.2 for those 75 years and older. Residents of long-term care facilities, a distinct subpopulation of elderly people, are at particularly high risk for developing nursing-home acquired pneumonia. Health costs for this sector are growing at an accelerated rate as the age of dea th increases. Thirteen percent of the population is over the age of 65 in the United States and this is expected to increase to 20% by 2030. In Canada, the proportion of individuals over the age of 65 is expected to rise to 20% in the year 2021. Presently, while making up 12% of the Canadian population, older adults account for 31% of acute hospital days and half of all hospital stays. To meet their health-care needs and alleviate the burden onthe health-care system, we must improve our understanding of the management and prevention of pneumonia in this age group. Elderly people constitute an ever-increasing proportion of the population. CAP has traditionally been recognized as problems that particularly affect the older individuals. According to western studies, the overall rate of pneumonia requiring hospitalization increase with age, from 1 per 1,000 persons in the general population but increases to 12 per 1,000 persons for those over age 75 years3. As the population of those ov er age 65 years is predicted to rise from its current level of 11% to 25 % of the total population in the year 20504, respiratory tract infection will assume a greater degree of importance to the overall public health. In Hong Kong, pneumonia was the fourth leading death from a specific diagnosis in 2001. A total of 3026 people died of pneumonia in 2001 which 1526 cases were male. Out of the 3026 deaths, 2794 patients were 65 or older which accounted for more than 90% of the total death. Pneumonia in the elderly population is a major cause of morbidity and mortality and in some series represents the leading cause of death. The annual cost of treating patients age > 65 years with pneumonia to be $4.8 billion, compared with $3.6 billion for those 85 years need help with bathing and 10% need help in using the toilet and transferring. The present of any or all of following identifies elderly persons at greatest risk for functional decline: pressure ulcer, cognitive impairment, functiona l impairment, and low level of social activity. The attack rate for pneumonia is highest among those in nursing homes. It is found that 33 of 1,000 nursing home residents per year required hospitalization for treatment of pneumonia, compared with 1.14 of 1,000 adults living in the community. Pneumonia is a major cause of morbidity and mortality worldwide. In the UK as a whole, pneumonia is responsible for over 10% of all deaths (66,581 deaths in 2001), the majority of which occur in the elderly. Community-acquired pneumonia (CAP) remains a common cause of morbidity. Because CAP also is a potentially fatal disease, even in previously healthy persons, early appropriate antibiotic treatment is vital. In Japan, pneumonia is the fourth leading cause of death, and from 57 to 70 persons per 100,000 populations died per year of this disease in the last decade. Community acquired pneumonia (CAP) is a leading infectious disease cause of death throughout the world, including Hong Kong, Pneumonia is the second most common infectious disease in Thailand. Whereas diarrhea is more common, pneumonia is associated with more fatalities. CAP remains the leading cause of death due to infectious diseases, with an annual incidence ranging 1.6-10.6 per 1,000 adult populations in Europe According to the Ministry of Health Malaysia (MOH), pneumonia is the 5th cause of death in Malaysia and the 4th cause of hospitalization. A prospective observational study by Jae et al (2007) of 955 cases of adult CAP in 14 hospitals in eight Asian countries found that the overall 30-day mortality rate was 7.3%. A prospective study by Liam CK et al (2001) of 127 cases of CAP in Malaysia found that the Mortality from CAP is more likely in patients with comorbidity and in those who are bacteraemic. A prospective study by LOH et al (2004) of 108 cases of adult CAP in urban-based university teaching hospital in Malaysia found that the mortality rate from CAP in hospital was 12%. 2.1.4 Syndromes of CAP The presence of various signs and symptoms and physical findings varies according to the age of the patients, therapy with antibiotics before presentation, and the severity of illness. Patients with pneumonia usually present with cough (>90%), dyspnea (66%), sputum production (66%% pleuritic chest pain (50%), and chills is present in 40-70% and rigor in 15%. However, a variety of nonrespiratory symptoms can also predominate in pneumonia cases, including fatigue (91%), anorexia (71%), sweating (69%), and nausea (41%). Metlay et al. (1997c) divided 1812 patients with CAP into four age groups: 18 through 44 years (43%), 45 through 64 years (25%), 65 through 74 years (17%), and 75 years or older (15%). For 17 of the 18 recorded symptoms there were significant decreases in reported prevalence with increasing age (p 37 °C at presentation. Crackles were present on auscultation in 80% of patients, and rhonchi in 34% to 47% (more common in the nursing home patients). About 25% had the physical findings of dullness to percussion, bronchial breathing, whispered pectoriloquy, and aegophony. Alteration in mental status was common. Marrie and coworkers (1989) reported confusion in 48% of the patients with nursing home-acquired pneumonia and in 30% of the other patients with CAP. Fine and colleagues (1998) define altered mental status as stupor, coma, or confusion representing an acute change from the usual state prior to presentation with pneumonia. This was present in 17.3% of the hospitalized patients. The decrease in symptoms with increasing age, tachypnea increased with increasing age (Metlay et al., 1997c). Thirty-six percent of 780 patients with CAP in the 18-44 year age group had tachypnea on admission versus 65% of the 280 patients who were = 75 years old. There were minimal differences in the proportion of patients with tachycardia and hyperthermia in the different age groups Pneumonia in the elderly are quite different from that in a younger population. These differences are due to age-related alterations in immunology, different epidemiology and bacteriology. It is important to remember that pneumonia in the elderly may report fewer respiratory signs and symptoms. The clinical presentation may be more subtle than in younger population, with more gradual onset, less frequent complaints of chill and rigors, and less fever. The classical finding of cough, fever, and dyspnea may be absent in over half of elderly patients8. Instead they may be manifest as delirium, a decline in f unctional status, weakness, anorexia, abdominal pain, or decrease general condition. The incidence of fever may decline with age, and the degree of fever appears lower in old population10. Tachypnea which respiration rate greater than 24-30 breaths per minute is noted more frequently in up to 69% of patients. Although rales are common and are noted in 78% of patients, signs of true consolidation are found in only 29%. Bacteremia, metastatic foci of infection and death are more frequent in older populations. As many elderly present with non-specific clinical symptoms and nonspecific functional decline that makes an accurate diagnosis difficult and may lead a life-threatening delay of diagnosis and therapy. Metlay et al. compared the prevalence of symptoms and signs of pneumonia in a cohort of 1812 patients and found that patients aged 65-74 years and over 75 years had 2.9 and 3.3 fewer symptoms, respectively, than those aged 18 through 44 years. The reduced prevalence of symptoms was most pronounced for symptoms related to febrile response (chills and sweats) and pain (chest, headache, and myalgia). These findings are consistent with those of Marrie et al. demonstrating reduced prevalence of non-respiratory symptoms among elderly patients. In a retrospective chart review by Johnson et al., the presence of dementia seemed to account for non-specific symptoms. However the sample size of the study was small and precluded a multivariable analysis. Roghmann et al found a significant inverse correlation between age and initial temperature in 320 older patients hospitalized for pneumonia. Evidence therefore does exist for a less distinct presentation of nonrespiratory symptoms and signs of pneumonia in the elderly. 2.1.5 Radiographic findings in CAP Radiographic changes usually cannot be used to distinguish bacterial from nonbacterial pneumonia, but they are often important for diagnosis of CAP, evaluating the severity of illness, determining the need for diagnostic studies, and selecting antibiotic agents. A chest radiograph usually shows lobar or segmental opacification in bacterial pneumonias and in the majority of atypical infections. Patchy peribronchial shadowing or more diffuse nodular or ground-glass opacification is seen less commonly, particularly in viral and atypical infections. The lower lobes are most commonly affected in all types of pneumonia. Small pleural effusions can be detected in about one-quarter of cases. Multilobar pneumonia is a feature of severe disease, and spread to other lobes despite appropriate antibiotics is seen in Legionella and M. pneumoniae infection. Hilar lymphadenopathy is unusual except in Mycoplasma pneumonia, particularly in children. Cavitation is uncommon but is a classic feature of S . aureus and S. pneumoniae infections. False negative results can be attributed to dehydration, evaluation during the first 24 hours, pneumonia due to Pneumocystis carinii, or pneumonia with profound neutropenia. 2.1.6 Etiology: More than 100 microorganisms have been identified so far as potential causative agents of CAP (Marrie 2001). They can be classified according to their biological characteristics as either bacteria, mycoplasma and other intracellular organisms, viruses, fungi and parasites. The most common causative agent of CAP is the bacteriumStreptococcus pneumoniae, which is implicated in 20% to 75% of cases of CAP (Marrie 2001) and about 66% of bacteremic pneumonia (Infectious Diseases Society of America 2000). Another causative bacterium is Haemophilus influenzae. So called â€Å"atypical† organisms have also been implicated as causal agents. These include Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila (Marrie 2001). Influenza is the most common serio Comparison of Pneumonia Management Methods Comparison of Pneumonia Management Methods INTRODUCTION 1.1 Background: Pneumonia is the inflammation and consolidation of lung tissue due to an infectious agent (Marrie TJ, 1994). Pneumonia has the highest mortality rate among infectious diseases and represents the fifth leading cause of death (Brandstetter, 1993). Pneumonia causes excess morbidity, hospitalization, and mortality, especially among the elderly, the fastest growing sector of the population.According to first- or second-listed diagnosis, approximately 1 million persons were discharged from short-stay hospitals after treatment for pneumoniain the United States in 1990, and elderly persons aged 65 years or more accounted for 52% of all pneumonia discharges (Fedson Musher, 1994). Pneumonia has the highest mortality rate among infectious diseases and represents the fifth cause of death (Brandstltter, 1993). In addition fine (2000) reported that lower respiratory tract infections affect three million persons annually and is the leading cause of death of infection in the United States. †¢ Pneumonia represented one of the 10th leading causes of hospitalization and deaths in Malaysia through 1999-2006 (Ministry of Health, Malaysia, 1999, 2000, 2001, 2002b, 2003, 2004, 2005band 2006b) Because of differences in pathogenesis and causative micro-organisms, pneumonia is often divided into: hospital acquired and community-acquired pneumonia.Community acquired pneumonia (CAP) is caused mainly by streptococcus pneumoniae. Its symptoms include coughing (with or without sputum production), change in colour of respiratory secretion, fever, and pleuritic chest pain (Fine, 2000). Nosocomial pneumonia or hospital acquired pneumonia is the second most common nosocomial infection in the United States and it causes the highest rates of morbidity and mortality. It is caused mainly by streptococcus pneumoniae and pseudomonas aeruginosa. The highest mortality rates occurred in patients with pseudomonas aeruginosa or acineobacter infection. It is characterized by fever and purulent respiratory secretion. Nosocomial pneumonia results in increase length of hospitalization and cost of treatment (Kashuba, 1999; Levison, 2003; Wilks et al., 2003). The clinical criteria for the diagnosis o f pneumonia include chest pain, cough, or auscultatory findings such as rales or evidence of pulmonary consolidation, fever or leucocytosis. In addition, there must be radiographic evidence, such as the presence of new infiltrates on chest radiograph, and laboratory evidence that supports the diagnosis. Because of differences in pathogenesis and causative micro-organisms, pneumonia is often divided in hospital acquired and community-acquired pneumonia. Pneumonia developing outside the hospital is referred to as community-acquired pneumonia (CAP). Pharmacoeconomic study Pharmacoeconomics is defined as the description and analysis of costs of drug therapy or clinical service to health care systems and society (Bootman et al., 1996). It has risen up as the discipline with the increase interst in calculating the value and costs of medicines (Sanches, 1994). Cost is defined as the value of resources consumed by the program or drug therapy of interest while a consequence is defined as the effect, outputs, or outcomes of a program. When identifying the costs associated with a product or service, all possible costs that include or related to the study are calculated (Sanchez, 1994). With the increase in financial pressure to hospitals to minimize their medical care costs, pharmacoeconomics can define costs and benefits of both expensive drug therapies and pharmacy based clinical services (Destache, 1993; Touw, 2005).Furthermore pharmacoeconomics can assist practitioners in balancing cost and quality that may result in improving patient care and cost saving to the institution (Sanches, 1994). Bootman and Harison (1997) stated that pharmacoeconomics and outcome research are very important to determine the efficient way to present a quality care at realistic rate. They suggested that pharmacoeconomics should have a remarkable authority on the delivery and financing of health care throughout the world. Different methods have been used to perform pharmacoeconomics analysis which includes: Cost-benefit analysis: Cost-benefit analysis two or more alternatives that do not have the same outcome measures. It measures all costs and benefits of a program in monetary terms (Bootman et al., 1996; Fleurence, 2003). Cost-benefit analysis could play a major role in identifying the specific costs and benefits associated with the pneumonia. Cost-effective analysis Cost-effective analysis compares alternatives that differ in safety, efficacy and outcome. Cost is measured in monetary terms, while outcome is measured in specific objectives or natural units. The outcome are expressed in terms of the cost per unit of success or effect (Bootman et al., 1996). Cost-utility analysis Cost-utility analysis compares treatment alternatives; benefits are measured in terms of quality of life, willingness to pay, and patient preference for one intervention over another, while cost is measured in monetary terms. It has some similarity to cost-effectivness with more concentration on patient view. As an example, looking for new druig therapy; benefits can built-in together with expected risks. Cost-minimization analysis Cost-minimization analysis is one of the simplest forms of pharmacoeconomics analysis. It is used when two or more alternatives are assumed to be equivalent in terms of outcomes but differ in the cost which is measured in monetary terms (Fleurence, 2003). Cost of illness analysis Cost of illness analysis is the determination of all costs of aparticular disease, which include both direct and indirect costs. Since both costs were calculated, an economic evaluation for the disease can be performed successfully. It has been used for evaluating many diseases (Bootman et al., 1996). 1.2 Study problems and rationale The management of pneumonia is very straight forward. However this is not always true for the diagnosis and selection of therapy. As there are some issues related to pneumonia that need to be addressed : The first issue pertains to the inappropriate diagnosis of the pneumonia. Some physicians do not properly identify the causative organism, I.e, whether, it is bacterial or viral. Bartlet et al (1998) found that the viral infections have been associated with at least 10% to 15 % of CAP in hospitalized adults (Bartlet et al, 1998). Secondly is the use of inappropriate medications. The prescription of inappropriate or un-indicated drug therapy such as the prescription of antibiotics for pneumonia caused by nonbacterial infection may increase the incidence of bacterial resistance (Steinman, 2003). Thirdly the adherence to guidelines improves quality of care and reduces the length of hospital stay (Marrie TJ et al, 2000). Fourthly the adherence to guidelines reduces the cost of treating pneumonia (Feagan BG, 2001). Fifthly Teaching hospitals are widely perceived to provide good outcome, and that reputation is thought to justify these institutions comparatively higher charges relative to non-teaching (general) hospitals. Despite their reputation for specialized care, teaching hospitals have traditionally relied on revenue from routine services, such as treatment of pneumonia, and the costs of specialized services and medical training. However, with managed care and competition creating pressures for cost containment, these higher costs have come into question: Do a teaching hospital provide good outcome for management of pneumonia, or do a general hospital provide comparable outcome at lower costs? 1.3 Significance of the Study This study has the following important issues: To the researchers: Several studies have compare the management of pneumonia in a university hospital versus a general hospital, but most of these studies were conducted in the USA and other parts of the world. There are no published studies in Malaysia or Asia to our knowledge. This study also provides the difference in the outcome, cost and cost-effectivness of treating pneumonia between a university hospital and a general hospital. To the practitioners: This study will provide information about the adherence to guidelines will reduce the length of hospital stay, reduce the cost of treating pneumonia and improve outcomes of treating pneumonia. To the patients: This study attempts to highlight the benefits associated with adherence to the guidelines. To the policy makers: This study will help policy makers to develop new strategies for management of pneumonia. This study will help policy makers to develop new guideline for management of pneumonia according to the microorganisms and the population in Malaysia. This study also provides the difference in the management of pneumonia between a university hospital and a general hospital. This study will provide information about how we can reduce the length of hospital stay, reduce the cost of treating pneumonia and improve outcomes of treating pneumonia. The results of this study will help in improving the management of pneumonia. It is the time to know whether a university hospital (H-USM) provide good outcome for treating pneumonia or do a general hospital (Penang-GH) provide comparable outcome at lower costs. By analyzing the cost and effectiveness of the regimens being used, the most effective therapy can be defined and the information can be offered to the policy makers to improve the deciosion making in treating pneumonia. The study will be able to help on: How we can make the drug therapy cost effective keeping effectiveness and outcome in our mind and try to suggest the best and most appropriate drug therapy which should be cost effective which help to decrease the financial burden on patients as well as Ministry Of health. This study will help to suggest how we can reduce the cost of therapy of treating pneumonia. The study will be able to provide data on: The incidence of pneumonia in (H-USM and Penang-GH). The most common organisms causing pneumonia in (H-USM and Penang-GH). The pattern of drugs used and management of pneumonia in in (H-USM and Penang-GH). The outcome of treating pneumonia in (H-USM and Penang-GH). The cost of treating pneumonia in (H-USM and Penang-GH). The cost-effectivness of treating pneumonia in (H-USM and Penang-GH). Whether a university hospital provide a good outcome for management of pneumonia, or a general hospital provide comparable quality at lower costs. 1.4 Hypothesis of the Study: H0: There is no significant difference of the management of pneumonia between a universiry hospital (H-USM) and a general hospital (Penang-GH). H1: There is a significant difference of the management of pneumonia between a universiry hospital (H-USM) and a general hospital (Penang-GH). 1.5 Aim of the study The aim of this study is to compare the management of pneumonia in a university hospital (H-USM) versus a general hospital (Pinanag-GH). 1.6 Objectives The objectives of this study are: To compare the incidence of pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the most common organisms associated with pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the drug therapy for pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the outcome of treating pneumonia (mortality rate, length of hospitalization, pneumonia related symptoms at discharge and complications of pneumonia) at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the cost of treating pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). To compare the cost-effectivness of treating pneumonia at a university hospital (H-USM) versus a general hospital (Penang-GH). 1.7 Research Questions What are the difference between the organisms that is commonly associated with pneumonia at H-USM and Penang-GH? What are the difference between the antibiotics that is commonly used for the treatment of pneumonia at H-USM and Penang-GH? What are the difference between the outcome of treating pneumonia (mortality rate, length of hospitalization, pneumonia related symptoms at discharge and complications of pneumonia) at H-USM and Penang-GH? What are the difference between the cost of treating pneumonia at H-USM and Penang-GH? And how can these costs be reduced? What are the difference between the cost-effectivness of treating pneumonia at H-USM and Penang-GH? Do a university hospital (H-USM) provide good outcome for treating pneumonia or do a general hospital (Penang-GH) provide comparable outcome at lower costs? CHPTER 2 LITERATURE REVIEW 2.1 Community-acquired pneumonia 2.1.1 Introduction Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, a new infiltrate on chest x-ray or auscultatory findings such as altered breath sounds and/or localized rales in community-dwelling patients (Infectious Diseases Society of America 2000). It is a common condition that carries a high burden of mortality and morbidity, particularly in elderly populations. Although most patients recover without sequellae, CAP can take a very severe course, requiring admission to an intensive care unit (ICU) and even leading to death. According to US data, it is the most important cause of death from infectious causes and the sixth most important cause of death overall (Adams et al. 1996). Even though the mortality from pneumonia decreased rapidly in the 1940s after the introduction of antibiotic therapy, it has remained essentially unchanged since then or has even increased slightly (MMWR 1995 ). Furthermore, significant costs are associated with the diagnosis and management of CAP. Between 22% and 42% of adults with CAP are admitted to hospital, and of those, 5% to 10% need to be admitted to an ICU (British Thoracic Society 2001). In the US, it is estimated that the total cost of treating an episode of CAP in hospital is about USD $ 7500, which is approximately 20 times more than the cost of treating a patient on an outpatient basis (Lave et al. 1999). CAP also contributes significantly to antibiotic use, which is associated with well-known problems of resistance. In treating patients with CAP, the choice of antibiotic is a difficult one. Factors to be considered are the possible etiologic pathogen, the efficacy of the substance, potential side-effects, the treatment schedule and its effect on adherence to treatment as well as the particular regional resistance profile of the causative organism and the co-morbidities that might influence the range of potential pathogens (such as in cystic fibrosis) or the dosage (as in the case of renal insufficiency). It may be a primary disease occurring at random in healthy individuals or may be secondary to a predisposing factor such as chronic lung disease or diabetes mellitus. CAP represents a broad spectrum of severity, ranging from mild pneumonia that can be managed by general practitioners outside the hospital to severe pneumonia with septic shock needing treatment in intensive care unit. Depending on severity of illness, about 20% of patients with pneumonia need hospitalization and approximately 1% of all CAP patients require treatment in ICU. Elderly persons and those with underlying conditions, such as cerebro and cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and alcoholism, are at increased risk for developing lower respiratory tract infections and complicated courses of infection. 2.1.2 Definition: Community-Acquired pneumonia (CAP) is defined as inflammation and consolidation of lung tissue induced by infectious microbes such as bacteria, viruses, or parasites. When the onset of symptoms and signs of this disease is before or within 48 hours after admission, it is considered as CAP (Bartlett JG et al., 1995). 2.1.3 Epidemiology Incidence: In the industrialized world, the annual incidence of CAP in community dwelling adults is estimated at 5 to 11 cases per 1000 adult population (British Thoracic Society 2001). The incidence is known to vary markedly with age, being higher in the very young and the elderly. In one Finnish study, the annual incidence for people aged 16-59 years was 6 cases per 1000 population, for those 60 years and older it was 20 per 1000, and for people aged 75 and over, 34 per 1000 (Jokinen et al. 1993). Annual incidences of 30-50 per 1000 population have been reported for infants below 1 year of age (Marrie 2001). Seasonal variations in incidence are also significant, with a peak in the winter months (Marrie 2001). The annual incidence of CAP requiring hospitalisation has been estimated at 1 to 4 patients per 1000 population (Marrie 1990, Fine et al. 1996). The proportion of patients requiring hospitalisation varies from country to country and across studies and has been estimated as ranging anywhe re between 15% and 56% (Foy et al. 1973, Minogue et al. 1998). Of those, 5% to 10% required admission to an intensive care unit (ICU) (British Thoracic Society Research Committee and Public Health Laboratory Service 1992, Torres et al. 1991). Conversely, about 8% to 10% of admissions to a medical ICU are due to severe CAP (Woodhead et al. 1985). Community acquired pneumonia (CAP) is a leading infectious disease cause of death throughout the world (WHO Statistical Information System (WHOSIS). WHO Mortality Database. Released: January 2005; Health, United States, 2005; Annual Report, Hong Kong, 2003/2004). Adult community-acquired pneumonia is a serious, life-threatening illness that affects more than 3 million people each year and accounts for more than half a million annual hospital admissions in the United States alone (Lynch JP, 1992). Each year, more than 900 000 cases of pneumonia occur in the United States, accounting for nearly 3% of all hospital admissions,(National Hospital Discharge Survey, 1988) and about 50 000 people die as a result of community-acquired pneumonia (Farr BM et al 203). Bartlet et al (1998) found that viral infections have been associated with at least 10% to 15 % of CAP in hospitalized adults. Adult community-acquired pneumonia is a serious, life-threatening illness that affects more than 3 million people each year and accounts for more than half a million annual hospital admissions in the United States alone. Each year, more than 900 000 cases of pneumonia occur in the United States, accounting for nearly 3% of all hospital admissions, and about 50 000 people die as a result of community-acquired pneumonia. In the USA, community acquired pneumonia is the fifth leading cause of death in people over the age of 65 years and an estimated 60 000 seniors die annually. Most of the excess deaths and hospitalizations due to lower respiratory infections occur in older adults, as reflected by the more than 44 000 hospitalizations for pneumonia and influenza in people aged 65 and older in 1997 in Canada. It is estimated that the age-specific incidence of pneumonia increases from 15.4 cases per 1000 in those aged 60-74 years to 34.2 for those 75 years and older. Residents of long-term care facilities, a distinct subpopulation of elderly people, are at particularly high risk for developing nursing-home acquired pneumonia. Health costs for this sector are growing at an accelerated rate as the age of dea th increases. Thirteen percent of the population is over the age of 65 in the United States and this is expected to increase to 20% by 2030. In Canada, the proportion of individuals over the age of 65 is expected to rise to 20% in the year 2021. Presently, while making up 12% of the Canadian population, older adults account for 31% of acute hospital days and half of all hospital stays. To meet their health-care needs and alleviate the burden onthe health-care system, we must improve our understanding of the management and prevention of pneumonia in this age group. Elderly people constitute an ever-increasing proportion of the population. CAP has traditionally been recognized as problems that particularly affect the older individuals. According to western studies, the overall rate of pneumonia requiring hospitalization increase with age, from 1 per 1,000 persons in the general population but increases to 12 per 1,000 persons for those over age 75 years3. As the population of those ov er age 65 years is predicted to rise from its current level of 11% to 25 % of the total population in the year 20504, respiratory tract infection will assume a greater degree of importance to the overall public health. In Hong Kong, pneumonia was the fourth leading death from a specific diagnosis in 2001. A total of 3026 people died of pneumonia in 2001 which 1526 cases were male. Out of the 3026 deaths, 2794 patients were 65 or older which accounted for more than 90% of the total death. Pneumonia in the elderly population is a major cause of morbidity and mortality and in some series represents the leading cause of death. The annual cost of treating patients age > 65 years with pneumonia to be $4.8 billion, compared with $3.6 billion for those 85 years need help with bathing and 10% need help in using the toilet and transferring. The present of any or all of following identifies elderly persons at greatest risk for functional decline: pressure ulcer, cognitive impairment, functiona l impairment, and low level of social activity. The attack rate for pneumonia is highest among those in nursing homes. It is found that 33 of 1,000 nursing home residents per year required hospitalization for treatment of pneumonia, compared with 1.14 of 1,000 adults living in the community. Pneumonia is a major cause of morbidity and mortality worldwide. In the UK as a whole, pneumonia is responsible for over 10% of all deaths (66,581 deaths in 2001), the majority of which occur in the elderly. Community-acquired pneumonia (CAP) remains a common cause of morbidity. Because CAP also is a potentially fatal disease, even in previously healthy persons, early appropriate antibiotic treatment is vital. In Japan, pneumonia is the fourth leading cause of death, and from 57 to 70 persons per 100,000 populations died per year of this disease in the last decade. Community acquired pneumonia (CAP) is a leading infectious disease cause of death throughout the world, including Hong Kong, Pneumonia is the second most common infectious disease in Thailand. Whereas diarrhea is more common, pneumonia is associated with more fatalities. CAP remains the leading cause of death due to infectious diseases, with an annual incidence ranging 1.6-10.6 per 1,000 adult populations in Europe According to the Ministry of Health Malaysia (MOH), pneumonia is the 5th cause of death in Malaysia and the 4th cause of hospitalization. A prospective observational study by Jae et al (2007) of 955 cases of adult CAP in 14 hospitals in eight Asian countries found that the overall 30-day mortality rate was 7.3%. A prospective study by Liam CK et al (2001) of 127 cases of CAP in Malaysia found that the Mortality from CAP is more likely in patients with comorbidity and in those who are bacteraemic. A prospective study by LOH et al (2004) of 108 cases of adult CAP in urban-based university teaching hospital in Malaysia found that the mortality rate from CAP in hospital was 12%. 2.1.4 Syndromes of CAP The presence of various signs and symptoms and physical findings varies according to the age of the patients, therapy with antibiotics before presentation, and the severity of illness. Patients with pneumonia usually present with cough (>90%), dyspnea (66%), sputum production (66%% pleuritic chest pain (50%), and chills is present in 40-70% and rigor in 15%. However, a variety of nonrespiratory symptoms can also predominate in pneumonia cases, including fatigue (91%), anorexia (71%), sweating (69%), and nausea (41%). Metlay et al. (1997c) divided 1812 patients with CAP into four age groups: 18 through 44 years (43%), 45 through 64 years (25%), 65 through 74 years (17%), and 75 years or older (15%). For 17 of the 18 recorded symptoms there were significant decreases in reported prevalence with increasing age (p 37 °C at presentation. Crackles were present on auscultation in 80% of patients, and rhonchi in 34% to 47% (more common in the nursing home patients). About 25% had the physical findings of dullness to percussion, bronchial breathing, whispered pectoriloquy, and aegophony. Alteration in mental status was common. Marrie and coworkers (1989) reported confusion in 48% of the patients with nursing home-acquired pneumonia and in 30% of the other patients with CAP. Fine and colleagues (1998) define altered mental status as stupor, coma, or confusion representing an acute change from the usual state prior to presentation with pneumonia. This was present in 17.3% of the hospitalized patients. The decrease in symptoms with increasing age, tachypnea increased with increasing age (Metlay et al., 1997c). Thirty-six percent of 780 patients with CAP in the 18-44 year age group had tachypnea on admission versus 65% of the 280 patients who were = 75 years old. There were minimal differences in the proportion of patients with tachycardia and hyperthermia in the different age groups Pneumonia in the elderly are quite different from that in a younger population. These differences are due to age-related alterations in immunology, different epidemiology and bacteriology. It is important to remember that pneumonia in the elderly may report fewer respiratory signs and symptoms. The clinical presentation may be more subtle than in younger population, with more gradual onset, less frequent complaints of chill and rigors, and less fever. The classical finding of cough, fever, and dyspnea may be absent in over half of elderly patients8. Instead they may be manifest as delirium, a decline in f unctional status, weakness, anorexia, abdominal pain, or decrease general condition. The incidence of fever may decline with age, and the degree of fever appears lower in old population10. Tachypnea which respiration rate greater than 24-30 breaths per minute is noted more frequently in up to 69% of patients. Although rales are common and are noted in 78% of patients, signs of true consolidation are found in only 29%. Bacteremia, metastatic foci of infection and death are more frequent in older populations. As many elderly present with non-specific clinical symptoms and nonspecific functional decline that makes an accurate diagnosis difficult and may lead a life-threatening delay of diagnosis and therapy. Metlay et al. compared the prevalence of symptoms and signs of pneumonia in a cohort of 1812 patients and found that patients aged 65-74 years and over 75 years had 2.9 and 3.3 fewer symptoms, respectively, than those aged 18 through 44 years. The reduced prevalence of symptoms was most pronounced for symptoms related to febrile response (chills and sweats) and pain (chest, headache, and myalgia). These findings are consistent with those of Marrie et al. demonstrating reduced prevalence of non-respiratory symptoms among elderly patients. In a retrospective chart review by Johnson et al., the presence of dementia seemed to account for non-specific symptoms. However the sample size of the study was small and precluded a multivariable analysis. Roghmann et al found a significant inverse correlation between age and initial temperature in 320 older patients hospitalized for pneumonia. Evidence therefore does exist for a less distinct presentation of nonrespiratory symptoms and signs of pneumonia in the elderly. 2.1.5 Radiographic findings in CAP Radiographic changes usually cannot be used to distinguish bacterial from nonbacterial pneumonia, but they are often important for diagnosis of CAP, evaluating the severity of illness, determining the need for diagnostic studies, and selecting antibiotic agents. A chest radiograph usually shows lobar or segmental opacification in bacterial pneumonias and in the majority of atypical infections. Patchy peribronchial shadowing or more diffuse nodular or ground-glass opacification is seen less commonly, particularly in viral and atypical infections. The lower lobes are most commonly affected in all types of pneumonia. Small pleural effusions can be detected in about one-quarter of cases. Multilobar pneumonia is a feature of severe disease, and spread to other lobes despite appropriate antibiotics is seen in Legionella and M. pneumoniae infection. Hilar lymphadenopathy is unusual except in Mycoplasma pneumonia, particularly in children. Cavitation is uncommon but is a classic feature of S . aureus and S. pneumoniae infections. False negative results can be attributed to dehydration, evaluation during the first 24 hours, pneumonia due to Pneumocystis carinii, or pneumonia with profound neutropenia. 2.1.6 Etiology: More than 100 microorganisms have been identified so far as potential causative agents of CAP (Marrie 2001). They can be classified according to their biological characteristics as either bacteria, mycoplasma and other intracellular organisms, viruses, fungi and parasites. The most common causative agent of CAP is the bacteriumStreptococcus pneumoniae, which is implicated in 20% to 75% of cases of CAP (Marrie 2001) and about 66% of bacteremic pneumonia (Infectious Diseases Society of America 2000). Another causative bacterium is Haemophilus influenzae. So called â€Å"atypical† organisms have also been implicated as causal agents. These include Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila (Marrie 2001). Influenza is the most common serio