Transcript Managing respiratory infections in primary care and emerging

Managing Respiratory Infections in Primary
Care and Emerging Antibiotic Resistance
David Enoch
Consultant Medical Microbiologist
Infection Control Doctor
Public Health England
Tuesday 3rd November
School of Clinical Medicine
What you need to know at the end of this talk
• Some of the problems of antimicrobial resistance
• Some local bacterial epidemiology
• Recommended treatment for common respiratory tract infections
The future is difficult to predict…
‘In another 20 years the Chest physician as the central figure of tuberculosis control will
also have disappeared. And by 2010 tuberculosis itself - with an incidence of 0.2 per
100,000 – will be of no more importance to the community than typhoid fever is today.
It will be of interest only to the medical historian.’
Bignall, 1971 Postgraduate Medical Journal
‘It is time to close the book on infectious diseases, and declare the war against
pestilence won.’
William H. Stewart, Surgeon General
The future is difficult to predict…
Emerging antibiotic resistance; carbapenemases
Emerging antibiotic resistance; carbapenemases
Good evidence that use
selects resistance
• Acquired resistance absent from bacteria
collected before 1940
• Resistance repeatedly followed
introduction of new antibiotics
• Resistant mutants selected in therapy
• Resistance greatest where use heaviest
Correlation between penicillin use and resistance
Goossens et al Lancet 2005
Good evidence that use selects resistance
Clostridium difficile
Antibiotic consumption UK
https://www.gov.uk/.../file/362374/ESPAUR_Report_2014__3_.pdf · PDF file
English surveillance programme for antimicrobial utilisation and resistance
Local data
www.edc.europa.eu
Local data
Antibiotic consumption UK 2011
www.edc.europa.eu
Most commonly used antibiotics (community)
•
•
β-lactams
– Penicillin V
– Amoxicillin
– Co-amoxiclav
– Flucloxacillin
Tetracyclines
– Tetracycline
– Doxycycline
•
Macrolides
– Clarithromycin
– Erythromycin
•
Antifolates
– Trimethoprim
Top five reasons for giving antibiotics (community)
• Respiratory tract infections
– Sore throat / pharyngitis
– Pneumonia
– Bronchitis
– (COPD)
– (Bronchiectasis)
– (Acute otitis media)
• Urinary tract infections
• Skin soft tissue infections (cellulitis)
Antibiotic guidelines
•
Based on national Clinical Knowledge Summary recommendations
http://www.cks.library.nhs.uk
•
Developed in conjunction with local microbiologists
•
Consider local susceptibility patterns
Antibiotic guidelines
Sore throat / pharyngitis
Sore throat / pharyngitis
•
Very common – 120 patients per year for a 2000 patient practice
• But only 1 in 18 episodes lead to a consultation
•
Viral infections are the commonest cause
• Common cold
(25%)
• Influenza
(4%)
• Adenovirus
(4%)
• Herpesvirus
(2%)
• EBV
(~1%)
Sore throat / pharyngitis
Sore throat / pharyngitis
•
Group A strep (GAS) is the commonest bacterial cause:
• 15-30% in children
• 10% in adults
•
Self limiting irrespective of whether or not viral
• within 3 days in 40% of cases
• within 7 days in 85% of cases
Sore throat / pharyngitis
Sore throat / pharyngitis – who will benefit from antibiotic treatment?
•
Cochrane collaboration 2007
• 27 studies involving 12,835 cases
• absolute benefit of antibiotics modest
• shortened duration of symptoms by 16 hours
• reduced incidence of suppurative complications
• quinsy, acute OM (by a third) and acute sinusitis (by 50%)
• natural history of symptoms similar in placebo group regardless of aetiology
•
Risk of complications with or without antibiotic is low for the majority of cases
•
•
Petersen et al 2007, UK cohort study
Number needed to treat to prevent quinsy = 4300 in patients with sore throat
Sore throat / pharyngitis
Sore throat / pharyngitis – who will benefit from antibiotic treatment?
•
Apply Centor criteria
• presence of tonsillar exudate
• presence of tender anterior cervical lymphadenopathy or lymphadenitis
• history of fever
• absence of cough
•
Centor 3 or 4 – 40-60% chance of Group A strep and may benefit from antibiotic
•
Centor 0 or 1 – unlikely to have Group A strep infection (80% chance) and antibiotics
is unlikely to be beneficial
Sore throat / pharyngitis
•
Who do you send a sample for?
Sore throat / pharyngitis
•
Who do you send a sample for?
•
UK and US guidelines differ somewhat…
Sore throat / pharyngitis
Scotland:
Throat swabs should not be carried out routinely in primary care management
of sore throat
• A positive throat culture for GAS makes the diagnosis of streptococcal sore
throat likely but a negative culture does not rule out the diagnosis
• Symptoms also correlate poorly with results of throat swab culture
• Throat swabs are neither sensitive nor specific for serologically confirmed
infection, considerably increase costs, may medicalise illness, and alter few
management decisions
SIGN guidelines (2010)
How should the diagnosis of GAS pharyngitis be established?
US guidelines
Swabbing the throat and testing for GAS pharyngitis by rapid antigen detection test (RADT) and/or culture
should be performed because the clinical features alone do not reliably discriminate between GAS and viral
pharyngitis except when overt viral features like rhinorrhoea, cough, oral ulcers, and/or hoarseness are
present
In children and adolescents, negative RADT tests should be backed up by a throat culture (strong, high).
Positive RADTs do not necessitate a back-up culture because they are highly specific (strong, high).
Routine use of back-up throat cultures for those with a negative RADT is not necessary for adults in usual
circumstances, because of the low incidence of GAS pharyngitis in adults and because the risk of subsequent
acute rheumatic fever is generally exceptionally low in adults with acute pharyngitis (strong, moderate).
Physicians who wish to ensure they are achieving maximal sensitivity in diagnosis may continue to use
conventional throat culture or to back up negative RADTs with a culture
Anti-streptococcal antibody titres are not recommended in the routine diagnosis of acute pharyngitis as they
reflect past but not current events; (strong, high)
Who Should Undergo Testing for GAS Pharyngitis?
USA
Testing for GAS pharyngitis usually is not recommended for children or adults with acute pharyngitis with
clinical and epidemiological features that strongly suggest a viral aetiology (e.g. cough, rhinorrhoea,
hoarseness, and oral ulcers; strong, high)
Diagnostic studies for GAS pharyngitis are not indicated for children <3 years old because acute rheumatic
fever is rare in children <3 years old and the incidence of streptococcal pharyngitis and the classic
presentation of streptococcal pharyngitis are uncommon in this age group
Selected children <3 years old who have other risk factors, such as an older sibling with GAS
infection, may be considered for testing (strong, moderate)
Follow-up post-treatment throat cultures or rapid antigen detection test (RADT) are not recommended
routinely but may be considered in special circumstances (strong, high)
Diagnostic testing or empiric treatment of asymptomatic household contacts of patients with acute
streptococcal pharyngitis is not routinely recommended (strong, moderate)
Shulman ST et al Clin Infect Dis. 2012; 55: e86-102
Rapid antigen detection tests (RADT)
Various results in meta-analyses
• Sensitivities between 59 and 95% and specificities over 90%
• Don’t differentiate between carriage and disease
• Take about 10 minutes
Wide variation in test methods
• Optical immunoassay
• ELISA
• FISH
• PCR
Wide variation in test performance
Wide variation in costs
Quality control
‘Insufficient evidence at present to support their use’ (SIGN 2010)
Sore throat / pharyngitis
Penicillin V
•
•
•
•
Narrow spectrum β-lactam agent
Main issue is erratic absorption – rapidly but incompletely absorbed
Has activity against streptococci including Group A streptococci
Not active against penicillinase producers
• Staphylococcus aureus
•
•
Only indicated for sore throat (pharyngitis)
Do not use in severe disease or in the systemically unwell
Acute chest infections
• Acute bronchitis
• acute inflammation of the bronchial tree associated with oedema and
mucus production leading to cough and phlegm production that lasts for
up to 3 weeks
• Community acquired pneumonia (CAP)
• acute infection of the lung parenchyma.
• Infective exacerbations of chronic obstructive pulmonary disease (COPD)
• Cough is the predominant symptom for acute bronchitis and communityacquired pneumonia (CAP)
• Difficult to distinguish CAP from acute bronchitis
Acute chest infections
Acute bronchitis
• Provide self-care advice: hydration, analgesia, and comfort measures. People who smoke
should be encouraged to quit
• Antibiotics are not routinely indicated
◦ Consider prescribing an antibiotic if the person has a significantly impaired ability to fight
infection (e.g. immunocompromised status, cancer, or physical frailty) or if acute bronchitis is
likely to significantly worsen a pre-existing condition (e.g. heart failure, angina, or diabetes)
If an antibiotic is necessary, prescribe amoxicillin first-line, or doxycycline as an alternative
Consider a macrolide (erythromycin or clarithromycin) if amoxicillin or doxycycline are
unsuitable
◦ A delayed antibiotic prescribing strategy may be considered
• Co-amoxiclav or doxycycline are options in people who have already received amoxicillin
CKS NICE guidelines
Community acquired pneumonia
Community- acquired Pneumonia
•
•
Key bacterial pathogens are
• Streptococcus pneumoniae
• Haemophilus influenzae
• Legionella pneumophila
• Staphylococcus aureus
• Atypicals
39%
5.2%
3.6%
1.9%
10.8%
Antibiotics are always indicated for patients with pneumonia
Respiratory tract infections
Table 1. Antibiotic susceptibility of S. pneumoniae
Organism
S. pneumoniae
% susceptible
Pen
Fluclox
Ery
Tetra
Cipro
94
-
81
89
-
Table 2. Antibiotic susceptibility of Gram-negative sputum isolates
Organism
H. influenzae
Moraxella catarrhalis
P. aeruginosa
% susceptible
Amox
80
10
-
Co-amox
96
99
-
Ery
97
-
Tetra
99
100
-
Cipro
98
99
78
Trim
82
-
Respiratory tract infections
Microbiological investigations
Usually not necessary to diagnose CAP or acute bronchitis managed in community.
Sputum samples for culture and/or sensitivity may be useful in people with:
• Recurrent episodes of acute bronchitis who may have become colonized with
bacteria resistant to first-line antibiotics.
Community acquired pneumonia
•
Use the CRB65 score to stratify patient’s risk of death
• CRB65 = 0:
low risk – treatment at home
• CRB65 = 1 or 2:
intermediate risk – consider same day assessment in hospital
• CRB65 = 3 or 4:
high risk – urgent admission
•
•
•
•
C – confusion
R – respiratory rate of ≥30 breaths/min
B – blood pressure — systolic of ≤90 mmHg or diastolic of ≤60 mmHg
≥65 years old
•
If available, use pulse oximetry to assess the severity of people with suspected pneumonia
and other acute respiratory illnesses
People with oxygen saturation less than 92% require admission to hospital
•
Community acquired pneumonia
Community-acquired Pneumonia
•
Choice of antibiotic
• Based on low prevalence of penicillin resistance among pneumococcus
•
First line
• CRB65 score of 0 – amoxicillin
• CRB65 score of 1 and at home – amoxicillin plus clarithromycin
•
Second line
• CRB65 score of 0 or 1 and at home – doxycycline (2nd line agent)
•
If no response at 48 hours in patients on amoxicillin
• Consider adding clarithromycin
Respiratory infections
•
What is the clinical evidence for single therapy treatment for CAP?
•
•
•
limited literature available for low severity CAP
only one RCT compared clarithromycin with or without cefuroxime
• no difference in mortality or complications reported
Amoxicillin is the current UK standard
• has advantage of amoxicillin over macrolides
• reduction in mortality
• fewer withdrawal from adverse events in studies
Respiratory infections
•
What is the clinical evidence for single therapy treatment for CAP?
•
Co-amoxiclav compared with clarithromycin
• more treatment discontinuation due to adverse event in the β-lactam arm
•
Azithromycin clinically favoured over erythromycin in one RCT
• mortality, clinical cure and withdrawal due to adverse events
Respiratory infections
•
Are there biomarkers you could use in General Practice to help differentiate
viral from bacterial LRTI?
Respiratory infections
•
Are there biomarkers you could use in General Practice to help differentiate
viral from bacterial LRTI?
•
Yes!
• CRP
• Procalcitonin
C-reactive protein (CRP)
Consider a point of care C-reactive protein test if after clinical assessment a
diagnosis of pneumonia has not been made and it is not clear whether antibiotics
should be prescribed
Use the results of the CRP test to guide antibiotic prescribing in people without a
clinical diagnosis of pneumonia as follows:
• Do not routinely offer antibiotic therapy if the CRP concentration is <20 mg/L
• Consider a delayed antibiotic prescription (a prescription for use at a later date if
symptoms worsen) if the CRP concentration is between 20 – 100 mg/L
• Offer antibiotic therapy if the CRP concentration is >100 mg/L
NICE guidelines
C-reactive protein and procalcitonin
Three RCTs examining the addition of CRP testing to usual care to guide antibiotic
prescription in patients presenting to primary care with LRTI were considered
These showed a significant reduction in antibiotic prescription rates in the CRP group
compared with usual care both at the index consultation and within 28 days
One systematic review examining the addition of PCT testing to usual care to guide
antibiotic prescription was considered. There was a significant reduction in antibiotic
prescription rates across all settings
CRP had a stronger correlation with consolidation on CXR than PCT or clinical
judgement alone
CRP is considerably cheaper than PCT (£12-15 compared with £25-35) when
considering the cost of tests
NICE guidelines
C-reactive protein and procalcitonin
Potential problems
• Costs
• Antibiotic course versus CRP test
• Reagents
• Who does the test?
• Quality assurance
NICE guidelines
COPD
Prescribe oral antibiotics for people with purulent sputum or clinical signs of
pneumonia depending on local antibiotic prescribing guidelines
◦Prescribe
or
amoxicillin 500 mg tds
doxycycline 200 mg, then 100 mg od
◦If amoxicillin and doxycycline are contra-indicated, prescribe
clarithromycin 500 mg bd
5 days
5 days
5 days
◦If the person has an increased risk of antibiotic resistance (comorbid disease,
severe chronic obstructive pulmonary disease [COPD], frequent exacerbations, or
antibiotic use in the past 3 months)
co-amoxiclav 500/125 mg tds
5 days
Differential diagnosis
If ‘acute bronchitis’ and cough persists longer than 3 weeks rule out:
• Asthma / chronic obstructive pulmonary disease.
• Post-infectious cough
• Whooping cough
• Post-nasal drip
• Gastro-oesophageal reflux
• Tuberculosis
• An underlying malignancy
Some cases (based on results)
Cases
Cases
Cases
Cases
Summary
Antibiotics are a precious resource
•
Community prescribing mostly for respiratory tract, urine and skin infections
•
Narrow spectrum antibiotics if possible
•
Short periods of treatment
•
Rapid / POCT may be worthwhile
•
Rationalise when possible, based on susceptibility results
•
Consider delayed prescribing where possible
•
If recurrent infections, address underlying source
Summary
Acknowledgements
Sani Aliyu
Fiona Cooke
Please remember that antibiotics are needed to treat infections…