Pneumonia (community-acquired): antimicrobial prescribing

The committee noted that using the care setting as a proxy for the severity of community-acquired pneumonia may not always be appropriate, and that some studies in outpatients may include people with moderate-severity community-acquired pneumonia, or a mixed severity population. They recognised that hospital admission criteria in other countries may differ from UK practice.

The committee discussed the pathogens which cause community-acquired pneumonia and noted that Streptococcus pneumoniae is the most common cause. Based on their experience, the committee noted that atypical pathogens are the causative organism in around 10% to 15% of moderate- to high-severity infections.

The committee discussed the evidence on choice of antibiotics in adults with low-severity community-acquired pneumonia and in adults with moderate- to high-severity community-acquired pneumonia.

The committee was aware that the CRB65 (in primary care) and CURB65 (in hospital) mortality risk scores were recommended in the NICE guideline on pneumonia in adults for assessing the risk of mortality with community-acquired pneumonia. The committee discussed evidence which used the pneumonia severity index to assess severity; however, they agreed that, when they can be calculated, CRB65 and CURB65 scores should be used in conjunction with clinical judgement to assess severity in adults.

Based on limited evidence showing no major differences in clinical effectiveness between antibiotics or classes of antibiotics, the committee agreed that the choice of antibiotic should largely be driven by their experience of which antibiotics have good activity against likely pathogens and cause the least harm, with as narrow spectrum as possible to minimise the risk of antimicrobial resistance. The committee considered the adverse effects associated with individual antibiotics, for example, increased risk of Clostridium difficile infection, along with the risk of harm from not adequately treating the infection.

Based on their experience, the first-choice antibiotic for adults with low-severity community-acquired pneumonia is amoxicillin (a penicillin), which has good activity against Streptococcus pneumoniae and is associated with fewer adverse effects and relatively low resistance rates. Amoxicillin is routinely used as first-line treatment and the committee agreed that there was no evidence to support changing current practice.

Alternative antibiotics are doxycycline (a tetracycline), clarithromycin (a macrolide) and erythromycin (an alternative macrolide in pregnancy), for people with low-severity community-acquired pneumonia and penicillin allergy, or when amoxicillin may not be appropriate, for example, if an atypical infection is suspected. These antibiotics have good activity against Streptococcus pneumoniae; however, because of their broader spectrum of activity (and because some of them also have additional safety warnings), the committee agreed that these antibiotics should be used only when there is a clinical reason not to use amoxicillin.

The committee discussed the MHRA Public Assessment Report on the safety of macrolide antibiotics in pregnancy. This found that the available evidence is insufficient to confirm with certainty whether there is a small increased risk of birth defects or miscarriage when macrolides are taken in early pregnancy. They agreed with the UK Teratology Information Service monograph on the use of macrolides in pregnancy. They decided that there should be an informed discussion of the potential benefits and harms of treatment. Then, after such a discussion, macrolides can be used if there is a compelling clinical need and there are no suitable alternatives with adequate pregnancy safety data. Erythromycin is the preferred choice if a macrolide is needed during pregnancy, for example, if there is true penicillin allergy and the benefits of antibiotic treatment outweigh the harms. This is because there is more documented experience of its use than for other macrolides.

Although evidence for doxycycline was not identified in people with low-severity community-acquired pneumonia, the committee agreed that evidence identified in hospitalised adults could include a mixed severity population. From its experience, the committee agreed that doxycycline is an appropriate choice as an alternative to a macrolide.

The committee discussed the evidence of effectiveness for azithromycin. However, it agreed that because of its long half-life and therefore increased likelihood of resistance, it was a less suitable choice than other macrolides.

From its experience, the committee agreed that although the available evidence does not differentiate between people with moderate-severity disease and those with high-severity disease, there is a clinical distinction between these groups which require different treatment options. Therefore, separate recommendations on antibiotic choice were made for moderate-severity and high-severity community-acquired pneumonia.

The committee recognised that there was not clear evidence that the addition of a macrolide to amoxicillin was effective for treating moderate- to high-severity community-acquired pneumonia in adults, although this was current routine practice. However, the committee had concerns about the consistency and quality of the evidence identified.

Based on their experience, the first-choice antibiotic for adults with moderate-severity community-acquired pneumonia is amoxicillin (a penicillin), with the addition of a macrolide if an atypical pathogen is suspected. Choices of macrolides are clarithromycin or erythromycin (in pregnancy). The committee based this decision on its experience of current practice, and because dual therapy with amoxicillin plus a macrolide provides broader spectrum of activity which is more likely to target atypical pathogens. In this population when the causative pathogen is not known, the risk of adverse effects and increased antimicrobial resistance with dual therapy is likely to be outweighed by the clinical benefit.

Based on its experience, the committee agreed that if dual therapy with amoxicillin plus a macrolide is given to people with moderate-severity community-acquired pneumonia, this should be reviewed when microbiological results are available. Microbiological results may be useful to guide a decision to stop the macrolide, helping to reduce the risk of resistance and adverse effects with dual therapy.

Alternative antibiotics for adults with moderate-severity community-acquired pneumonia and penicillin allergy are doxycycline (a tetracycline) or clarithromycin (a macrolide) alone. This is based on the committee's experience that these antibiotics have good activity against Streptococcus pneumoniae, as well as atypical infections. The committee noted that there are no reasonable alternatives for dual therapy in adults who are unable to take a penicillin, for example, due to penicillin allergy.

The committee discussed evidence that fluoroquinolone monotherapy (levofloxacin or moxifloxacin) was as effective as beta-lactam plus macrolide dual therapy for people with moderate- to high-severity community-acquired pneumonia. However, they noted the safety concerns with fluoroquinolones, such as tendon damage and aortic aneurysm. The committee noted that the licence is restricted in community-acquired pneumonia, and agreed that fluroquinolones should only be used when other medicines cannot be prescribed or have been ineffective.

The committee agreed that if first and alternative antibiotic choices are not appropriate for adults with low- or moderate-severity community-acquired pneumonia, clinical judgement or seeking specialist advise from a local microbiologist is appropriate.

Based on its experience, the first-choice antibiotic for adults with high-severity community-acquired pneumonia is co‑amoxiclav (a penicillin with a beta-lactamase inhibitor) with clarithromycin or erythromycin (in pregnancy). This provides broad-spectrum gram-negative cover and cover for atypical pathogens. The high risk of mortality in this population outweighs the potential adverse effects and increased risk of antimicrobial resistance with broad-spectrum antibiotics.

The alternative antibiotic for adults with high-severity community-acquired pneumonia and penicillin allergy is levofloxacin. The committee discussed the evidence of effectiveness for levofloxacin and recognised that Legionella pneumophila infection is more common in this population. The committee agreed that the high risk of mortality without appropriate treatment in this population outweighs the safety concerns and therefore agreed that levofloxacin monotherapy is an appropriate alternative.

The committee discussed the evidence that doxycycline is as effective as levofloxacin for adults with moderate- to high-severity community-acquired pneumonia. However, the evidence for doxycycline comes from 1 small study with a 0% mortality rate, suggesting this is not a high-severity population. Therefore, the committee agreed that there is insufficient evidence to recommend doxycycline for this population.

The committee agreed that people with high-severity community-acquired pneumonia and penicillin allergy, in whom a fluoroquinolone is not appropriate, is likely to be a small population and specialist microbiological advice should be sought.

The committee was not aware of any validated severity assessment tools for children and young people with community-acquired pneumonia. The committee agreed that features which suggest severe community-acquired pneumonia in children and young people include difficulty breathing, oxygen saturation less than 90%, raised heart rate, grunting, very severe chest indrawing, inability to breastfeed or drink, lethargy and reduced level of consciousness. The severity of symptoms and signs should be assessed by clinical judgement, taking into account these features.

Based on the evidence identified and its experience, the committee agreed that it was appropriate to make separate recommendations for non-severe and severe community-acquired pneumonia.

Given the specialist expertise needed for treatment of children under 1 month with community-acquired pneumonia, the committee agreed that these children should have their treatment managed by a paediatric specialist.

Overall, the committee agreed there was limited evidence relevant to UK practice, and that the evidence had major limitations.

Therefore, the committee agreed that the choice of antibiotics in children and young people should largely be driven by its experience of which antibiotics have good activity against likely pathogens and cause the least harm, with as narrow spectrum as possible to minimise the risk of antimicrobial resistance.

The committee discussed evidence that co‑amoxiclav was more effective than amoxicillin for children with non-severe community-acquired pneumonia. However, the committee noted that this was based on 1 small RCT within a systematic review, and a lower than expected response rate to amoxicillin was reported compared with other studies in children, which may have been due to sub‑therapeutic dosing.

Based on their experience, the first-choice antibiotic for children and young people with community-acquired pneumonia and non-severe symptoms or signs is amoxicillin, which is effective against the most common causative pathogens and is well tolerated. The committee also recognised the clinical experience of the effectiveness of amoxicillin in children and young people, and its common use in current practice.

Alternative antibiotics are clarithromycin, erythromycin (in pregnancy) and doxycycline (in young people aged 12 to 17 years only) for children and young people with non-severe symptoms or signs and penicillin allergy, or if amoxicillin is unsuitable (for example, if an atypical pathogen is suspected). These antibiotics have good activity against Streptococcus pneumoniae; however, because of their broader spectrum of activity, the committee agreed that these antibiotics should only be used when there is a clinical reason not to use amoxicillin.

The committee agreed that if first and alternative antibiotic choices are not appropriate for children and young people with non-severe community-acquired pneumonia, clinical judgement or seeking specialist advice from a local microbiologist is appropriate.

The committee highlighted that the evidence identified for children and young people with severe community-acquired pneumonia was conducted in low-income countries, where severe pneumonia may be more common. The committee was aware that children with severe community-acquired pneumonia in the UK will usually have underlying respiratory conditions. Therefore, the evidence identified may not be directly relevant to UK practice.

Based on its experience, the first-choice antibiotic for children and young people with severe community-acquired pneumonia is co‑amoxiclav, with the addition of clarithromycin or erythromycin (in pregnancy) if an atypical pathogen is suspected. The committee discussed that children and young people with severe symptoms or signs are likely to be at higher risk of treatment failure with amoxicillin, and therefore need broader-spectrum antibiotics to target a range of possible causative organisms. Antibiotics to cover atypical pathogens should also be available if atypical infection is suspected. In this population when the causative pathogen is not known, the risk of adverse effects and increased antimicrobial resistance with dual therapy is likely to be outweighed by the clinical benefit.

The committee agreed that children and young people with severe community-acquired pneumonia and penicillin allergy is likely to be a small population and specialist microbiological advice should be sought.

The committee recognised that community-acquired pneumonia is potentially a life‑threatening infection and that a person's condition may change rapidly.

The committee agreed that advice should be given to adults, young people and children about:

They agreed that adults, young people and children should be reassessed if symptoms or signs do not improve as expected or worsen rapidly or significantly. If symptoms or signs have not improved following antibiotic treatment, a microbiological sample should be sent for testing if this has not been done already to help guide further treatment. The committee was aware that obtaining a microbiological sample may not always be possible.

The committee was aware that community-acquired pneumonia can be caused by a viral infection and therefore agreed that during reassessment, non-bacterial causes of community-acquired pneumonia, such as infection with flu, should be taken into account.

The committee was aware of recommendations from NICE guidelines on pneumonia in adults and sepsis that cover when to refer people to hospital.

The committee agreed by consensus that adults with any symptoms or signs suggesting a more serious illness or condition or, with symptoms that are not improving as expected with antibiotics, should be referred to hospital if they are being treated in the community.

The committee recognised that not all children and young people need to have their treatment managed in hospital, and referral should be based on clinical judgement because no evidence was identified. They agreed that community-acquired pneumonia is less common in children and young people, and that referral to hospital should be considered, or specialist paediatric advice on further investigation and management should be sought.