Scholarly article on topic 'Community-acquired pneumonia in northern Australia: low mortality in a tropical region using locally-developed treatment guidelines'

Community-acquired pneumonia in northern Australia: low mortality in a tropical region using locally-developed treatment guidelines Academic research paper on "Biological sciences"

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Abstract of research paper on Biological sciences, author of scientific article — Julian H. Elliott, Nicholas M. Anstey, Susan P. Jacups, Dale A. Fisher, Bart J. Currie

Summary Objective: To investigate the epidemiology and outcome of adult community-acquired pneumonia (CAP) in tropical Australia. Methods: A prospective study was performed of all adult patients with CAP admitted to the Royal Darwin Hospital, a major hospital in tropical northern Australia. A standard definition of CAP was used and data collected on demographics, risk factors, history, examination, investigations, treatment and outcome. Locally-developed treatment guidelines were used. Results: One hundred and sixty-seven adults were included in the analysis. Aboriginal people were over-represented, younger and were more likely to have risk factors for CAP. The most frequent pathogens isolated were Streptococcus pneumoniae and Burkholderia pseudomallei. ‘Atypical pneumonia’ organisms were uncommon. Treatment guidelines included penicillin for mild pneumonia but emphasised coverage of Burkholderia pseudomallei in those with risk factors, especially during the monsoon season. The mortality rate from pneumonia was low with three deaths in 167 cases (1.8%). Conclusions: International guidelines for the management of CAP have been based on populations and organisms from temperate regions and may not necessarily be applicable to tropical regions. Guidelines based upon local epidemiology must therefore be developed. This study illustrates how mortality can be minimised using a process of determining local CAP etiology, developing treatment guidelines and auditing patient management.

Academic research paper on topic "Community-acquired pneumonia in northern Australia: low mortality in a tropical region using locally-developed treatment guidelines"

International Journal of Infectious Diseases (2005) 9, 15—20

ELSEVIER

Community-acquired pneumonia in northern Australia: low mortality in a tropical region using locally-developed treatment guidelines

Julian H. Elliotta,c, Nicholas M. Ansteya,b, Susan P. Jacupsb, Dale A. Fishera, Bart J. Curriea b *

aRoyal Darwin Hospital and Northern Territory Clinical School, Flinders University, Darwin, Australia

bMenzies School of Health Research, Charles Darwin University, P.O. Box 41096,

Casuarina, Northern Territory 0811, Darwin, Australia

cCurrently National Centre in HIV Epidemiology and Clinical Research,

University of New South Wales, Sydney, Australia

Received 12 March 2003; received in revised form 25 July 2004; accepted 8 September 2004 Corresponding Editor: Patricia Munoz, Madrid, Spain

Summary

Objective: To investigate the epidemiology and outcome of adult community-acquired pneumonia (CAP) in tropical Australia.

Methods: A prospective study was performed of all adult patients with CAP admitted to the Royal Darwin Hospital, a major hospital in tropical northern Australia. A standard definition of CAP was used and data collected on demographics, risk factors, history, examination, investigations, treatment and outcome. Locally-developed treatment guidelines were used.

Results: One hundred and sixty-seven adults were included in the analysis. Aboriginal people were over-represented, younger and were more likely to have risk factors for CAP. The most frequent pathogens isolated were Streptococcus pneumoniae and Burkholderia pseudomallei. 'Atypical pneumonia' organisms were uncommon. Treatment guidelines included penicillin for mild pneumonia but emphasised coverage of Burkholderia pseudomallei in those with risk factors, especially during the monsoon season. The mortality rate from pneumonia was low with three deaths in 167 cases (1.8%).

Conclusions: International guidelines for the management of CAP have been based on populations and organisms from temperate regions and may not necessarily be applicable to tropical regions. Guidelines based upon local epidemiology must there-

* Corresponding author. Tel.: +61 8 89228056; fax: +61 8 89275187. E-mail address: bart@menzies.edu.au (B.J. Currie).

INTERNATIONAL SOCIETY

FOR INFECTIOUS DISEASES

http://intl.elsevierhealth.com/journals/ijid

KEYWORDS

Aborigine; Australia;

Community-acquired

pneumonia; Tropical; Melioidosis; Guidelines

1201-9712/$30.00 © 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2004.09.008

fore be developed. This study illustrates how mortality can be minimised using a process of determining local CAP etiology, developing treatment guidelines and auditing patient management.

© 2005 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Introduction

Worldwide, lower respiratory tract infections are the major cause of death1 and they are an increasing cause of death in industrialised countries.2 Guidelines for the management of community-acquired pneumonia (CAP) have been written for resource-limited settings3 and for temperate industrialised countries.1'4-6 In regions such as tropical northern Australia and tropical 'middle-income' countries there is an unique combination of the availability of resource-intensive treatments and tropical epidemiology. There is a need to develop guidelines for the management of CAP in these regions based upon appropriate evidence. The unique epidemiology and high mortality rate of bacteremic CAP in people admitted to the Royal Darwin Hospital (RDH) located in the tropical north of Australia has been previously documented (Table 1). The hospital's guidelines for the treatment of CAP were developed in response to these data. To investigate CAP treatment outcomes in this setting a prospective study of all patients admitted over a 12-month period was performed.

Methods

Royal Darwin Hospital (RDH) is the only tertiary referral hospital for the tropical areas of the Northern Territory. It serves a population of around 150,000 (25% Aboriginal) living across an area of 516,945 km2. Royal Darwin Hospital has the only intensive care unit in the region and so patients requiring management of severe CAP must be transferred to RDH. This study did not include patients admitted to the local private hospital or the two small regional hospitals unless they were transferred to RDH.

Patients were eligible for inclusion if they were admitted to RDH between 1 March 1999 and 29 February 2000, aged 13 years or older, diagnosed with pneumonia within 24 hours of admission, had a new pulmonary infiltrate on chest X-ray and had confirmatory clinical findings. These were specified as at least one major criterion of cough, sputum production or fever greater than 37.8 °C or at least two minor criteria of pleuritic chest pain, dyspnoea, altered mental status, consolidation on examination or white cell count greater than 12 x 109/L. Patients were excluded if they had been hospitalised within the previous two weeks, the pneumonia was related to lung carcinoma or tuberculosis or if the presentation was found on review to be due to an alternative etiology. Severity of illness was graded as mild, moderate or severe by the treating physician.

Antibiotic treatment was given according to the RDH guidelines for the treatment of adult community-acquired pneumonia. Penicillin was used for mild to moderate cases and ceftriaxone for severe cases, with the exception of patients with moderate or severe pneumonia and risk factors for melioidosis (infection with Burkholderia pseudomallei) or Aci-netobacter pneumonia (excess alcohol intake, diabetes, chronic lung disease, chronic renal failure, steroid therapy or excess kava intake). In these patients ceftriaxone and gentamicin were used. The former is included because of its activity against B. pseudomallei, the latter because of its activity against Acinetobacter.7,8 During the monsoon 'wet season', the risk of melioidosis in patients with these risk factors increases substantially and so ceftriaxone was replaced by ceftazidime for patients admitted to the general ward with moderate pneumonia and by meropenem for patients admitted to the intensive care unit.9 These provide improved coverage against B. pseudomallei. The

Table 1 Adult community-acquired bacteremic pneumonia: Royal Darwin Hospital 1986—1998.

255 cases 84 deaths (33%) Admissions Deaths Mortality by organism Percentage

Number of cases Percentage of total admissions Number of total deaths Percentage of total deaths

Streptococcus pneumoniae 100 39% 17 20% 17%

Burkholderia pseudomallei 60 24% 30 36% 50%

Staphylococcus aureus 29 11°% 11 13% 38%

Acinetobacter baumannii 26 10°% 14 17% 54%

'wet season' is defined as the six-month period between December and May, inclusive. At the treating physician's discretion coverage for 'atypical pneumonia' organisms was added, usually with a macrolide.

Microbiological investigations were standard as performed by the treating physician. Microbiological etiology was defined as follows: positive growth in blood culture apart from growth of S. epidermidis or mixed organisms; pure culture of an organism collected in sputum if there were >25 leukocytes/low power field and <10 epithelial cells/low power field during microscopy; culture of an organism recovered from a sterile site such as pleural fluid or pleural or lung biopsy; culture of B. pseudomallei from any site; greater than four-fold rise in serology titer or initial titer of 1:160 or higher or convalescent titer of >1:320; or positive viral polymerase chain reaction.

A data collection form was designed that included information on demographics, risk factors, history, examination, investigations, treatment and outcome. Patients were prospectively enrolled in the study and relevant information collected by one of the investigators. Data were transferred to a computerised database (Access, Microsoft) and analysed using Stata (StataCorp, USA). Comparisons of ethnicity and risk factors with the regional population were made using population ethnicity and risk factor data from the Australian Bureau of Statistics.8 Statistical significance was determined by use of the x2 test with a P-value cut-off of less than or equal to 0.05. Comparison of continuous variables was performed using the Student's t-test. Overall mortality was defined as death during admission to hospital. Attributable mortality was defined as death during admission to hospital due to CAP as assessed by one of the investigators (JE). Approval for the study was granted by the Joint Institutional Ethics Committee of the Royal Darwin Hospital and the Menzies School of Health Research.

Results

One hundred and sixty-seven adults admitted to the Royal Darwin Hospital fulfilled the criteria for community-acquired pneumonia and all were included in the analysis. Ninety-four (56.3%) were male. The age range was 13-90 years with a median age of 45 years. Six patients were aged 13-15 years and two aged 16 years. The residence of patients reflected the demographics of the 'top end' of the Northern Territory with 100 (59.9%) coming from urban areas, 51 (30.5%) from rural areas and 15 (9.0%) from outside the Northern Territory.

Four (2.4%) patients were residents of nursing homes and 14 (8.4%) were immunosuppressed. Five

were taking long-term prednisolone, one had chronic myeloid leukaemia and two each had HIV infection, renal transplants, systemic lupus erythe-matosus and previous splenectomy. Forty-six patients (27.5%) consumed excess alcohol, 41 (24.6%) were current smokers and two (1.2%) were current injecting drug users.

Aboriginal people were over-represented with 80 (47.9%) patients identifying as aboriginal compared to the population from which admissions were drawn, where approximately 20% identify as aboriginal (P < 0.001). Aboriginal people included in the study were more likely to have risk factors for CAP (Table 2). These included a documented previous episode of CAP, bronchiectasis, chronic renal failure, diabetes and excess alcohol intake. Compared to the aboriginal population from which admissions are drawn,10 the rates for excess alcohol intake and chronic renal failure were significantly higher (P < 0.001). The rate of diabetes was no higher than the regional aboriginal population. The rate of bronchiectasis was not able to be compared to the population prevalence as this is not known. The rates of cigarette smoking, chronic obstructive pulmonary disease, cardiac failure and pneumococ-cal vaccination were not significantly different between Aboriginal and non-Aboriginal patients.

A microbiological diagnosis was achieved in 38 (22.8%) cases (Table 3). In 20 (52.6%) cases this was despite a negative blood culture. For both blood culture positive and negative groups the most frequent pathogens isolated were Streptococcus pneu-moniae and B. pseudomallei. A small number of other bacterial and viral pathogens were isolated. There were no cases of the 'atypical pneumonia' organisms Mycoplasma pneumoniae, Chlamydophila (formerly Chlamydia) pneumoniae, legionellosis, psittacosis or Q fever identified amongst the 16 patients who had serology specifically performed for these. Agents active against these organisms were used in 41 (24.6%) initial regimens and 17 (10.2%) subsequent regimens.

No high-level penicillin resistance was detected in clinical isolates of S. pneumoniae during the study period. Reduced sensitivity (MIC 0.1-1.0 mg/L) was detected in 20% of isolates. The remainder were fully sensitive to penicillin (MIC <0.1 mg/L). Season was only a significant factor in the likelihood of isolation of B. pseudomallei. All six cases were identified during the 'wet season' (P = 0.03).

Treatment included intensive care support in 15 (9.0%) cases. Nine (5.4%) patients required intubation, four (2.4%) non-invasive respiratory support and five (3.0%) inotropic agents. Nine (5.4%) patients developed a para-pneumonic effusion or empyema. Twelve (7.2%) patients suffered deterioration in renal

Table 2 Median age, risk factors for CAP and outcome in Aboriginal and non-Aboriginal patients with community-acquired pneumonia: Royal Darwin Hospital March 1999—February 2000.

Aboriginal patients Non-aboriginal patients P-value

(N = 80) N (%) (N = 87) N (%)

Mean age (years) 47.2 49.4 0.46

Median age (years) 47.5 45.0

Pneumococcal vaccination 14 (17.5) 5 (5.7) 0.02

Previous CAP 27 (33.8) 9 (10.3) <0.001

Alcohol excess 32 (40.0) 14 (16.1) 0.001

Smoker 22 (27.5) 19 (21.8) 0.42

COPDa 26 (32.5) 26 (29.9) 0.75

Asthma 12 (15.0) 18 (20.7) 0.36

Bronchiectasis 8 (10.0) 0 (0) 0.002

Chronic renal failure 15 (18.8) 2 (2.3) <0.001

End-stage renal disease 5 (6.3) 1 (1.2) 0.08

Diabetes 21 (26.3) 9 (10.3) 0.008

Previous stroke 0 (0) 3 (3.4) 0.09

Malignancy 0 (0) 2 (2.3) 0.18

Immunosuppression 5 (6.3) 9 (10.3) 0.41

Injecting drug use 0 (0) 2 (2.3) 0.17

Liver dysfunction 12 (15.0) 6 (6.9) 0.09

Cardiac failure 19 (23.8) 12 (13.8) 0.10

Death 2 (2.5) 1 (1.1) 0.50

a COPD: chronic obstructive pulmonary disease.

function, but only one (0.6%) required dialysis. Twenty (12.0%) patients remained febrile five days after admission and commencement of antibiotics, but subsequently recovered fully.

Using the guidelines for the treatment of community-acquired pneumonia described above, the mortality rate attributed to pneumonia was low with three deaths in 167 cases (1.8%). All of these

Table 3 Proportion of diagnostic procedures with positive isolation and description of micro-organisms.

Site Proportion with positive result (%) Organism Number positive (%)

Blood 18/132 (13.6) S. pneumoniae 9 (5.4)

B. pseudomallei 5 (3.0)

P. aeruginosa 2 (1.2)

K. pneumoniae 1 (0.6)

S. aureus 1 (0.6)

Sputum 17/98 (17.3) S. pneumoniaeb 6 (3.6)

B. pseudomalleic 4 (2.4)

P. aeruginosac 3 (1.8)

S. aureusc 1 (0.6)

H. influenzaeb 3 (1.8)

Bronchial wash 2/4 (50.0) B. pseudomalleid 1 (0.6)

RSV PCR positive 1 (0.6)

Pleural tap 4/11 (36.4) B. pseudomalleid 3 (1.8)

Mixed anaerobes 1 (0.6)

Pleural biopsy 1/1 (100) B. pseudomallei 1 (0.6)

Lung biopsy 1/1 (100) M. tuberculosis 1 (0.6)

Serology 3/16 (18.8) Influenza Ae 3 (1.8)

Sputum PCRa 1/1 (100) Varicella 1 (0.6)

a PCR: polymerase chain reaction.

b Sputum culture of S. pneumoniae and H. influenzae was only accepted if the sputum was of good quality (>25 leukocytes/low power field and <10 epithelial cells/low power field), the Gram stain showed predominance of Gram-positive cocci (in the case of S. pneumoniae) or Gram-negative bacilli (in the case of H. influenzae) and the culture was a pure growth.

c Six patients with positive sputum cultures had positive blood cultures: B. pseudomallei 3, P. aeruginosa 2, S. aureus 1. d Positive cultures were also obtained for B. pseudomallei from other sites.

e One patient with a titer of 1:160 on admission and two patients with titers of >1:320 on convalescent samples.

patients had multiple chronic medical conditions including cardiac failure and two had dialysis-dependent renal failure. Only one of these three patients had a microbiological cause identified, with S. pneumoniae isolated from blood. Two additional patients not included in the study were dead on arrival at the hospital due to pneumonic melioidosis and two patients with pneumonia on admission to the hospital died from other causes.

Discussion

Documenting the etiology and outcome of community-acquired pneumonia is problematic due to the difficulty in obtaining microbiological diagnoses and defining disease in non-severe cases. This study was limited to hospitalised patients and so does not include a description of the mild disease able to be treated in the community on an outpatient basis. Nevertheless, this series is reasonably representative of people in the region hospitalised with CAP given that most patients are admitted to RDH.

The rate of microbiological diagnosis achieved in this study is similar to other studies using routine clinical diagnostic techniques. Approximately half of these diagnoses were achieved through the use of blood cultures. Regardless of the method of isolation the most important pathogens were S. pneu-moniae and B. pseudomallei. The latter was seen almost exclusively during the monsoon period and was the most important pathogen during this time of the year. In a prospective study of melioidosis it was shown that 50% of melioidosis presentations are with CAP, of which 52% are bacteremic.11 No clinical factors other than season were predictors of CAP due to B pseudomallei. By comparison, the epidemiology of CAP during the 'dry season' was similar to most temperate areas of the world, with predominance of S. pneumoniae. The absence of any S. pneumoniae isolates with high-level resistance to penicillin supports the current Australian antibiotic guidelines, which continue to recommend penicillin for the treatment of CAP in certain circumstances.

Compared to other areas of Australia12 and elsewhere in the world13—15 the impression of clinicians working in tropical Australia has been that organisms traditionally associated with 'atypical' pneumonia are uncommon in the region. The data here are consistent with this, with none of these organisms identified during the 12 months. This is also consistent with a previous study of CAP in tropical Australia,16 although serology was not performed often enough in either study to determine the true proportion of pneumonias caused by these organisms. In other years, cases of mycoplasma have been confirmed at

RDH and during the study year there were several cases in the community and at the local private hospital. Psittacosis and legionellosis (usually Legionella longbeachae) have also occasionally been diagnosed at RDH. In order to better define the role of 'atypical pneumonia' organisms in various tropical locations including northern Australia, local studies should be performed with prospective collections of convalescent sera for specific serological assays. However the very low mortality rate in this study supports the validity of the current local guidelines, which leave the option of adding antibiotic cover for 'atypical pneumonia organisms,' to the discretion of the treating physician, while emphasising the importance of B. pseudomallei and A. baumannii cover for defined circumstances.

In the past, melioidosis has been documented at RDH as the most common cause of fatal adult bac-teremic CAP.9 Early appropriate antibiotics are important in minimising the mortality in melioidosis and the present guidelines have been associated with a halving of melioidosis mortality at RDH.9 Similarly, this study shows a reduction in blood culture positive CAP mortality following revision of the RDH CAP antibiotic guidelines in 1999 from 84/255 (32.9%) prior to revision to 1/18 (5.6%) postrevision (P = 0.015). It is suggested that similar processes of identification of local CAP epidemiology, development of practice guidelines and audit of the use of such guidelines are important steps in improving the care of people with CAP in settings where guidelines from societies in industrialised countries or from international organisations such as the WHO are likely to be of limited relevance. The RDH CAP guidelines are now incorporated into Australian CAP guidelines as recommendations for the treatment of CAP acquired in tropical Australia.17

The demographic characteristics of this series are more similar to those of developing countries than series from Europe or USA. This study describes a relatively young median age, a low rate of immuno-suppressive conditions or injecting drug use and a relatively high proportion of people from rural areas and of indigenous background. However, an important difference from many developing countries is the continuing low rate of HIV in the population. The high rate of chronic medical conditions is also similar to the rapidly urbanising populations of many 'middle-income' countries. In this setting, in a tropical region, a low mortality rate has been achieved for hospitalised patients with CAP using a locally developed, season-specific antibiotic protocol and intensive care support when necessary. The low mortality rate and incomplete data on arterial blood gas concentrations preclude the comparison of these data with those used to develop CAP grading scales such as the Pneu-

monia Severity Index (PSI).18 In contrast with the extensive work on grading of CAP in children in developing countries,19 there are relatively few data to inform risk stratification in adults with CAP in resource-limited and/or tropical settings. In the absence of more appropriate scales at the time of this study, severity of disease was graded by treating physicians as mild, moderate or severe. The PSI has recently been adapted for use in tropical Australia using the data presented here and from earlier stu-dies20 and is included in the current national guidelines for the management of CAP in tropical areas.17 This study documents the increased burden of severe lower respiratory tract infections in the Aboriginal people of tropical Australia. They were over-represented in the overall number of admissions, were younger and were more likely to have had previous episodes of CAP. These findings also indicate the importance of chronic conditions in Aboriginal adults predisposing to CAP, particularly chronic lung disease, chronic renal failure and excess alcohol intake. In addition to traditional approaches made to reduce the burden of acute respiratory infections, such as improvement in environmental conditions and pneumococcal and influenza vaccination, attempts to reduce the burden of lung disease in Aboriginal people should include interventions targeting preventable chronic disease, including cigarette smoking, diabetes, chronic renal failure and excess alcohol consumption.

In summary, treatment guidelines for CAP based upon local epidemiology have been developed for tropical northern Australia, where melioidosis has been an important cause of mortality. This study illustrates how mortality can be minimised using a process of determining local CAP etiology, developing treatment guidelines and auditing patient management and outcomes.

Conflict of interest: No conflict of interest to declare.

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