Use of a treatment protocol in the management of community-acquired lower respiratory tract infection

Fahad A. Al-Eidana, James C. McElnaya,*, M. G. Scottb, M. P. Kearneyc, J. Corrigand and J. B. McConnelld

a Pharmacy Practice Research Group, School of Pharmacy, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL; b Antrim Hospital Academic Pharmacy Practice Unit, Antrim Area Hospital; c Department of Microbiology, United Hospital Group Trust; d Department of Medicine, Antrim Area Hospital, Bush Road, Antrim BT41 2RL, UK

Abstract

The aim of the present study was to examine the impact of an antimicrobial prescribing protocol on clinical and economic outcome measures in hospitalized patients with community-acquired lower respiratory tract infection (LRTI). The study was performed as a prospective controlled clinical trial within the medical wards at Antrim Area Hospital, Northern Ireland. Data were collected on all hospitalized adult patients with a primary diagnosis of LRTI during the period December 1994 to February 1995 (normal hospital practice; control group; n = 112). After an LRTI management protocol (medical, microbiological and pharmacy staff) had been developed, all hospitalized adult patients with a primary diagnosis of LRTI over the period December 1995 to February 1996 formed the intervention group (treated according to the protocol; n = 115). The results showed a statistically significant impact of the protocol in terms of clinical and economic outcome measures. Patients treated using the algorithmic prescribing protocol had significant reductions in length of hospital stay (geometric mean 4.5 versus 9.2 days), iv drug administration (34.8% versus 61.6%), duration of iv therapy (geometric mean 2.1 versus 5.7 days) and treatment failures (7.8% versus 31.3%). Healthcare costs were also significantly reduced. The use of the protocol was a major factor in streamlining the prescribing of antimicrobial therapy for community-acquired LRTI and led to more cost-effective patient management.

Introduction

Most types of respiratory tract infection are self-limiting; however, lower respiratory tract infections (LRTIs), such as community-acquired pneumonia (CAP) and infective exacerbations of chronic obstructive airways disease (COAD), are still associated with high rates of hospitalization, morbidity and mortality.1 The incidence of community-acquired LRTI in the UK in 1993 was 44 cases per 1000 population. The incidence has been found to be age related, ranging from 8.1 cases per 1000 in the 16–19 year old age group to 121.5 per 1000 in patients aged 70–79 years old.2 LRTIs occur more commonly in smokers and the incidence doubles during the winter months.3

Determination of the main features of the disease is important to guide decisions regarding hospital admission, admission to intensive care and the route of antimicrobial administration. Studies by the British Thoracic Society,4 subsequently confirmed by Farr et al.5 and Karalus et al.,6 showed a 21-fold increase in the risk of death or the need for intensive care unit management when two or more of the following three factors are present: (i) respiratory rate >30/min; (ii) diastolic blood pressure <60 mm Hg; (iii) serum urea >7 mmol/L.

The overall mortality from LRTI in hospitalized patients is 6.7–18% in British populations, accounting for about ten times as many deaths as all other infectious diseases combined.4 CAP is potentially more serious, with elderly people and those with pre-existing illness at greatest risk of dying.7 Data published in 1984 indicated that worldwide an estimated 2.2 million people died each year as a result of acute respiratory infections, making these infections, along with diarrhoeal diseases, the leading international cause of preventable death.8

LRTIs account for a substantial proportion of total public health costs, of which admission to hospital is one of the most important cost factors. The healthcare costs associated with treating LRTI may be decreased by controlling the incidence of hospital admissions,9 length of hospitalization, number of diagnostic tests used and number of therapeutic interventions undertaken.10,11 Length of hospitalization is a key cost determinant and therefore identifying hospitalized patients who are suitable for early conversion from parenteral to oral antimicrobial therapy can shorten the duration of hospital stay and thereby reduce the healthcare cost per patient. Empirical therapeutic intervention may reduce the number of diagnostic tests performed, but may increase drug acquisition costs because of the use of broad-spectrum antimicrobials to cover all possible causative organisms.12 Extensive diagnostic testing is, however, more likely to be reserved for cases where the diagnosis of pneumonia or infective exacerbation of COAD is difficult.

The aim of the present study was to collect baseline data on the current management of community-acquired LRTI and to develop an antimicrobial prescribing protocol for the treatment of hospitalized patients with LRTI. A further aim was to examine the impact of this protocol on a range of patient outcome measures, e.g. length of hospital stay and treatment success. A final goal was to assess the economic impact of the introduction of the prescribing protocol.

Materials and methods

Study site

The research was performed in the medical wards of Antrim Area Hospital, a 378 bed teaching hospital in Northern Ireland.

Patients and treatments

All adult patients with a primary diagnosis of LRTI admitted to the medical wards of Antrim Area Hospital during the period December 1994 to February 1995 formed the control group on which baseline data were collected. Diagnoses were made on clinical grounds, with or without radiological evidence. These patients received empirical treatment for their condition, i.e. before the development of the prescribing protocol. The severity of pneumonia in this group was assessed using the scoring system detailed below.

All consecutively admitted adult patients with a primary diagnosis of LRTI (see above) over the period December 1995 to February 1996 formed the intervention group, i.e. they were treated according to an agreed protocol (FigureGo), which was developed via close collaboration between physicians, microbiologists and clinical pharmacists. The protocol was introduced in November 1995. It considered the severity of the infection, with a score of one point given for each of the following if present: age >60 years; respiratory rate >30 breaths/min; diastolic blood pressure <60 mm Hg; WBC >20 or <4 x 109 cells/L; new confusion; new atrial fibrillation; multiple lobe involvement on X-ray.13 The LRTI was deemed moderate if the overall score was two or less, severe if the score was three or more and very severe if the score was three or more and the patient was also suffering from hypoxaemia (pO2 < 8 kPa on 28% oxygen). In the protocol group, treatment depended on severity of the infection. According to the agreed protocol, moderate infection was treated using oral amoxycillin/ clavulanic acid 375 mg every 8 h, severe infection was treated with iv cefuroxime 1.5 g every 8 h, and very severe infection was treated using iv cefuroxime 1.5 g every 8 h and iv erythromycin 1 g every 6 h. Erythromycin was also recommended when atypical infection was considered likely or if the patient was allergic to penicillin (clarithromycin was an alternative if erythromycin was poorly tolerated). In severe and very severe cases the following criteria were applied to switch patients from iv to oral therapy: patient able to tolerate oral preparations; cough, sputum and respiratory distress improving; patient afebrile; WBC count normalizing.14–16 The number of factors to be improved and the extent of the improvement before switching were left to clinical judgement. An opt-out clause was included in the protocol to allow consultant opinion and sensitivity results to be addressed if required. There were no other changes in the standard of care over the 2 year study period.



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Figure. Algorithm for the treatment of hospitalized patients with community-acquired pneumonia.

 
Protocol introduction

All consultant physicians (no changes during the study period) within the medical directorate were involved in the construction of the protocol and supported its use. Before the implementation of the protocol three steps were taken to promote its use:

Data collection and outcome measures

Control and intervention patients (Table IGo) were followed during their complete hospital stay and, to allow therapeutic and economic comparisons to be made between the two groups, details were recorded for each patient as follows: age, gender, allergic status, out-patient status (admission from nursing home or community), length of time between onset of illness and admission to hospital, length of hospital stay, treatment duration and modalities, treatment success, signs and symptoms of infection (as per outlined scoring system), severity of illness, and biochemistry, haematology, microbiology and radiology reports during the hospital stay. In respect of radiology, reports were made in the normal way and were available within a few hours for interpretation by clinicians. A customized data collection form was used to record this information.


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Table I. Patient demography
 
In assessing therapeutic outcomes, the following definitions were agreed by the research team:

In retrospect, it is recognized that a separate scoring system for assessing the success or failure of a particular treatment would have been beneficial.

Pharmacoeconomic analysis

The economic analysis was limited to three main healthcare costs, i.e. total antimicrobial costs (antimicrobial acquisition costs and hidden costs, including cost of consumable materials, staff time and waste disposal), diagnostic test costs and hospital bed costs. All costs were calculated for the total hospital stay (using March 1996 prices).

Statistical analysis

Paradox (Version 3.5) software was used for data entry whereas statistical analyses were performed using SPSS (Version 7). Differences between control and protocol groups were analysed using the {chi}2 test and Fisher's exact test for categorical variables as appropriate. Student's t test was used for continuous variables. A logarithmic transformation to base 10 was performed to normalize the outcome measures data (length of hospital stay, duration of iv administration, duration of treatment in hospital and elements of healthcare costs) and to calculate confidence intervals for means.17 Results are reported as statistically significant at P < 0.05.

Results

A total of 227 patients was assessed during the study (112 control patients and 115 protocol patients). Details of the patients in the two groups are included in Table IGo. The vast majority of patients in both groups were admitted from their domiciliary residence (92.9% and 90.4% respectively in the control and protocol groups) and the remaining patients were admitted from nursing or residential homes. There was no significant difference in the patients' living arrangements before admission (P > 0.05; {chi}2 test). Furthermore, there were no significant differences (P > 0.05) between the two groups regarding patient age and gender. The mean onset time (i.e. the number of days of illness before admission) was almost identical between the two groups at approximately 5 days (Table IGo). Signs and symptoms on admission (fever, cough, sputum, tachypnoea and tachycardia) did not differ between the two groups (P > 0.05, {chi}2 test). The severity of disease also did not differ significantly (P > 0.05; {chi}2 test) between the two groups. The proportion of patients who scored three or more was 31% in the control group and 35% in the protocol group. Although the mortality rate appeared higher in the control group (8.0% versus 3.5%) this was not significantly different (P > 0.05; {chi}2 test).

A range of laboratory tests were used in both control and protocol patients (Table IIGo). The only statistically significant difference detected between the groups regarding laboratory tests was the fact that a higher percentage of patients in the protocol group had a sputum culture ordered (P < 0.05; {chi}2 test). The results obtained from these tests were, however, not significantly different (P > 0.05; {chi}2 test). The most frequently isolated organism was Streptococcus pneumoniae, which was isolated in approximately 35% of patients. No significant growth in the sputum cultures was observed in about 42% of cases. Less commonly isolated organisms were Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus, and in two cases in the protocol group Haemophilus parainfluenzae was isolated. Chest X-ray data obtained for both groups of patients were also very similar and did not differ significantly (P > 0.05; {chi}2 test). White blood cell counts, serum creatinine and blood urea were also similar (P > 0.05; t test) in the two groups (Table IIGo). There were no changes in reporting of sensitivities from the microbiological laboratory during the study periods.


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Table II. Laboratory findings
 
A wide range of antimicrobials were used in the control group (cefuroxime, cefotaxime, erythromycin, co-amoxiclav, ampicillin, amoxycillin, penicillin, clarithromycin, ofloxacin, flucloxacillin, ciprofloxacin and tetracycline) whereas only three agents (cefuroxime, erythromycin and co-amoxiclav) were used in the protocol group. Intravenous cefuroxime was given to all patients who were considered to have a severe infection (see FigureGo) whereas erythromycin (oral) was given to those patients who were considered to have an atypical pneumonia, on clinical grounds. All usage of co-amoxiclav was via the oral route. The number of initial treatment failures was much lower in the protocol group (7.8% versus 31.3%; 95% confidence interval (CI) of the difference, 13.6–33.4%; P < 0.001; {chi}2 test; Table IIIGo).


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Table III. Treatment failures and causes
 
There were also highly significant differences in the treatment duration in hospital, with the number of days (geometric mean) almost doubled in the control group (8.8 days versus 4.5 days; P < 0.001; unpaired t test; Table IVGo). This decreased length of treatment was largely due to the initial use of oral antimicrobial and patients being ‘switched’ early from iv to oral therapy as per the protocol, therefore permitting earlier discharge of patients. Patients' length of hospital stay (geometric mean) in the protocol group was 4.5 days compared with 9.2 days in the control group (P < 0.001; unpaired t test). The number of patients receiving iv antimicrobials was also reduced in the protocol group (40% versus 69%; P < 0.001; {chi}2 test), as was the duration (geometric mean) of iv therapy (2.1 versus 5.7 days; P < 0.001; unpaired t test). All patients in the protocol group were followed up at 28 days to ensure that early discharge did not have a detrimental effect on their clinical outcome. No treatment failures were identified.


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Table IV. Outcome measures
 
Economic data are presented in Table VGo. The decreased length of hospital stay contributed to substantial decreases in the overall cost (geometric mean; adjusted to March 1996 prices) of hospitalization per patient (£1020 versus £2024; P < 0.001; unpaired t test). Laboratory test costs were slightly higher, but not statistically so, in the protocol group. This was due largely to appropriate requests for sputum cultures. The costs of antimicrobials (including hidden costs, e.g. consumable materials used in drug preparation and delivery) were approximately five times higher in the control group (geometric mean; £53.7 versus £10.7; P < 0.001; unpaired t test).


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Table V. Economic outcome measures
 
Discussion

Healthcare systems around the world are attempting to minimize costs and at the same time improve overall quality of care by developing and implementing the most cost-effective treatment regimens. Following introduction of a treatment protocol for community-acquired LRTIs in the study site hospital, the healthcare costs decreased significantly with a concomitant improvement in the outcome measures, e.g. number of treatment failures decreased. The success of the protocol method of management of community-acquired LRTIs was due to three main contributing factors: (i) the scoring system adapted from risk factors drawn up by the British Thoracic Society;13 (ii) the introduction of sequential therapy with oral antimicrobials when a patient's condition had been stabilized or was improving according to predetermined criteria; (iii) the clear presentation of the algorithm approach to infection management (see FigureGo). Undoubtedly the care with which hospital physicians were introduced to the protocol (seminar and on-ward discussions) helped ensure full adherence to the protocol. The scoring system, based on identified risk factors, was a useful guide in severity classification, antimicrobial prescribing and determination of the route of administration. This system was able to decrease the incidence of iv administration from 61.6% in the control group to 34.8% in the protocol group, i.e. a difference of 26.8% (95% CI of the difference was 14.3–39.4%). During this period, no patients were placed in the very severe group. The protocol was useful for junior doctors to use without having to wait for a more senior physician. Thus the diagnosis of chest infection could be made by the admitting doctor with the patient being assessed subsequently by a consultant. It is recognized, however, that because of the high percentage of patients scoring two or less in both groups that admission criteria should be reviewed, especially in the light of the success achieved in the present study with oral co-amoxiclav.

In this study criteria adapted from Quintiliani et al.,14 Allen et al.15 and Ramirez et al.16 were used to assist the prescribing physicians in their decision to convert patients from iv to oral therapy. Although all other criteria had to be met, WBC counts were not routinely determined before the sequential therapy was commenced. By using this method, the length of iv therapy and length of hospital stay were significantly reduced (P < 0.001).

Aetiological organisms involved in control and intervention groups were similar. In both groups S. pneumoniae was responsible for the largest proportion of isolates, accounting for approximately 35% of sputa cultured; this figure is within the range of 30–70% reported by other investigators.18,19 The second largest number of isolates was for H. influenzae (15.1%) followed by M. catarrhalis (4.4%), i.e. the proportions of isolated organisms were similar to reports by others.9,20

Length of hospital stay was the most expensive aspect of patient healthcare in this study, as has been reported by others.21,22 As expected, there has been a general trend of decreased hospital stay in the study site hospital over time; however, during the period of the study, length of hospital stay fell by only 19%, which is low when compared with the 51% decrease seen after introduction of the protocol. The decreased length of stay led to an average saving per patient treated in the protocol of £1004. The savings resulted from decreased antimicrobial acquisition costs, hidden costs, costs of biochemistry, haematology and radiology tests, and hospital bed costs. There was no saving attributed to microbiology tests costs, because the protocol encouraged treating physicians to perform microbiology tests such as sputum and blood cultures for patients within the protocol group. The availability of these test results is likely to have encouraged adherence to later aspects of the protocol. The present study adds weight to the findings of a recent study conducted in Dublin23 in which the researchers concluded that the use of oral antimicrobials is at least as efficacious as iv therapy, and led to decreased costs as a result of patients being discharged earlier from hospital.

A further development, which has resulted from the current investigation, is the placement of the algorithm on the hospital intranet with severity scoring being performed automatically in response to questions posed on-screen. In addition, work is continuing on how case-mix variations influence outcomes and on the development of guidelines for use in the primary care setting to facilitate decision- making regarding the need for hospitalization of patients with LRTI.

Acknowledgments

We are grateful to medical colleagues who co-operated with this study and permitted their patients to be included. We are also grateful for statistical advice from Dr C. Patterson, Department of Epidemiology and Public Health, The Queen's University of Belfast.

Notes

* Corresponding author. Tel: +44-1232-335800; Fax: +44-1232-247794; E-mail: j.mcelnay{at}qub.ac.uk Back

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Received 26 March 1999; returned 8 July 1999; revised 20 August 1999; accepted 2 November 1999