Transcript Document

Pneumonia & Respiratory Tract Infection:
Antibiotic risk for Clostridium difficile
Kieran Hand*, Adil Ahmed†, Adriana Basarab¶, Whitney Chow†, Nick Cortes¶ & Sally Pearce*
*Pharmacy Department, †Department of General Medicine, ¶Microbiology Department
Southampton University Hospitals NHS Trust
Table 2. Outcomes by PTWR diagnosis and risk group of PTWR antibiotic regimen
Introduction
 Respiratory tract infections (RTI), including community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive
pulmonary disease (AECOPD) and aspiration pneumonia are a leading cause of hospital admission and result in considerable
morbidity and mortality.
 Antibiotics generally recommended for treatment of RTI are however, also implicated in the development of Clostridium difficile
infection (CDI)1,2.
 In response to a comparatively high incidence of CDI in a large university teaching hospital, antibiotic treatment guidelines were
revised in November 2007 to promote prescribing of antibiotics considered low-risk for predisposing patients to CDI.
PTWR
diagnosis
CAP
(nonsevere)
CAP
(severe)
Objectives
 Evaluate clinical outcomes in patients treated with low-risk antibiotics compared to patients treated with high-risk antibiotics.
Antibiotic
risk (n)
Tmt.
failure
High (6)
Low (8)
Days to normalisation*
Length of
stay*
30-day
Survival
2 (0-9)
8 (6-8)
5 (83%)
4 (0-12)
9 (6-35)
6 (75%)
6 (5-7)
14 (5-23)
17 (4-29)
2 (67%)
5 (0-10)
4 (4)
5 (0-10)
12 (9-14)
2 (100%)
1 (0-7)
3 (1-7)
3 (1-12)
4 (1-11)
6 (100%)
1 (6%)
1 (0-31)
3 (0-31)
3 (0-31)
6 (0-30)
18 (100%)
High (2)
0
0
5 (2-8)
3 (0-5)
9 (4-14)
2 (100%)
Low (7)
1 (14%)
1 (0-1)
2 (0-6)
2 (0-3)
3 (1-31)
7 (100%)
High (2)
0
0
19 (3-35)
18 (0-35)
18 (2-34)
2 (100%)
Low (1)
0
0
14
14
19
1 (100%)
High (0)
N/A
N/A
N/A
N/A
N/A
N/A
Low (2)
0
0
0
0
7
1 (50%)
High (1)
0
0
0
2
36
1 (100%)
Low (0)
N/A
N/A
N/A
N/A
N/A
N/A
High (20)
5 (25%)
0 (0-7)
4 (0-35)
3 (0-35)
7 (1-36)
18 (90%)
Low (38)
6 (16%)
0 (0-31)
3 (0-31)
3 (0-31)
7 (0-35)
35 (92%)
Fever
CRP
WBC
2 (33%)
0 (0-3)
4 (2-9)
3 (38%)
1 (0-22)
4 (2-11)
High (3)
2 (67%)
5 (5)
Low (2)
1 (50%)
High (6)
1 (17%)
Low (18)
AECOPD
Method
 The new RTI guidelines (Table 1) were published on the hospital intranet and printed algorithms were distributed to the relevant
clinical areas. Junior doctors in the admissions unit and ward pharmacists received training and pharmacists promoted guideline
compliance.
LRTI
Pleural
effusion
Table 1. Antibiotic prescribing for respiratory tract infection (RTI)
Indication
CAP (severe)
CAP (non-severe)
AECOPD
Aspiration pneumonia
Any RTI (penicillin allergy)
New guideline
Benzylpenicillin +
(1st line Doxycycline or
2nd line Clarithromycin)
1st line Doxycycline or
2nd line Amoxicillin
1st line Doxycycline or
2nd line Amoxicillin
Metronidazole +
(1st line Doxycycline or
2nd line Amoxicillin)
Chloramphenicol or Doxycycline
Previous practice
Co-amoxiclav +
Clarithromycin
Lung
Fibrosis
Amoxicillin +
Clarithromycin
Co-amoxiclav
Aspiration
pneumonia
Co-amoxiclav
All RTI†
Cefuroxime or Clarithromycin
 Data were collected from consecutive RTI admissions to the hospital’s acute medical unit over a 2-week period in December 2007.
Ethics approval was not required. The diagnosis on the post-take ward round (PTWR) was considered the definitive diagnosis.
 During the weeks following the audit, case notes were reviewed to establish outcome data. If inflammatory markers had not
normalised on discharge, for the purposes of this analysis they were assumed to have normalised on the day following discharge.
 Treatment failure was defined as a change in PTWR antibiotic therapy other than a switch from intravenous to oral agents.
*Values presented as median (range) for surviving patients only. †Chi-square Treatment Failure p>0.1
High-risk antibiotics: Co-amoxiclav, amoxicillin, clarithromycin, cefuroxime
Low-risk antibiotics: Benzylpenicillin, doxycycline, chloramphenicol
Discussion and Conclusion

Results
 Sixty-four consecutive patients admitted with RTI were included in the study.
 Severity assessments were documented on admission for two of 33 suspected CAP cases.
 Retrospective severity scoring indicated that 24 had non-severe CAP but 13 of these were treated with antibiotic regimens
recommended for severe pneumonia.
 Of the 24 patients treated with antibiotics for AECOPD, only 7 had documented evidence of increased sputum purulence, the prerequisite for antibiotic therapy as recommended by the UK National Institute for Health and Clinical Excellence (NICE) 3.
 Table 2 summarises the results for 58 patients for whom clinical outcome data were available.
 First-line low-risk antibiotic regimens were used for two-thirds of patients (38/58) following the PTWR. No cases of Clostridium difficile
infection presented within a 30-day follow-up.
 Treatment failure rates for low-risk regimens appeared lower than for high-risk regimens for all RTI combined and all other outcome
measures appeared broadly comparable for low-risk and high-risk regimens.
 Median Charlson co-morbidity index score was 1.0 for both groups of patients - those who received high-risk antibiotics and those who
received low-risk antibiotics.




The results suggest a tendency amongst doctors to over-prescribe antibiotics for patients with AECOPD and to
overprescribe broad-spectrum antibiotic regimens for non-severe pneumonia.
This may reflect a lack of awareness of current guidelines and severity assessment algorithms or may indicate
defensive prescribing by inexperienced junior doctors.
The study has suggested a trend towards non-inferiority with regard to clinical outcomes in the treatment of RTI for
antibiotic regimens considered ‘low-risk’ for predisposing patients to Clostridium difficile infection compared to ‘highrisk’ regimens.
This study is exploratory and hypothesis-generating and a randomised controlled trial is required to confirm these
findings.
Treatment with ‘low-risk’ antibiotics appears to be comparable to standard treatment regimens in patients with
respiratory tract infection admitted to a large teaching hospital and may result in reduced incidence of Clostridium
difficile infection.
References
1.
2.
3.
British Thoracic Society. BTS Guidelines for the management of community-acquired pneumonia in adults. Thorax 2001;56 (suppl IV): 1-64.
Fowler S, Webber A, Cooper BS et al. Successful use of feedback to improve antibiotic prescribing and reduce Clostridium difficile infection: a
controlled interrupted time series. J Antimicrob Chemother 2007; 59(5):990-5.
NICE. Management of exacerbations of COPD. Thorax 2004; 59:131-156.