Treatment of pneumonias

01Definition and overview

The treatment of pneumonia has three jobs: to kill the organism with an antibiotic (or antiviral), to support the failing lung and the body until it recovers, and to find and treat complications. The antibiotic is chosen blind, because the organism is found in only a minority to a half of patients, and the result comes after treatment has begun. A good choice depends on the answers to four questions:

1. 1

   Where was it caught?

   Community, hospital (and how long after admission), or on a ventilator. The setting predicts the organisms and their resistance (the other topics of this chapter).
2. 2

   How severe is it?

   The CRB65 or CURB65 score, the oxygen need, and judgement. Severity sets the place of care, the route and the breadth of the antibiotic.
3. 3

   Is the patient at risk of a resistant or unusual organism?

   Recent antibiotics or hospital stay, colonisation by a multidrug-resistant organism, bronchiectasis, immunosuppression, aspiration, travel or exposure.
4. 4

   What are the patient's circumstances?

   Allergy, pregnancy, kidney and liver function, drug interactions (macrolides and QT-prolonging drugs, fluoroquinolones and corticosteroids), and whether they can take tablets.

02Etiology and pathophysiology

The pathogens the treatment has to meet

The classes of drug are described in pharmacology: the penicillins, the cephalosporins and the carbapenems and glycopeptides.

Why a drug fails

• No target. A β-lactam acts on the bacterial cell wall; Mycoplasma has no wall, and Legionella, Chlamydia and Coxiella live inside cells that β-lactams penetrate badly.
• Destruction of the drug. β-lactamases of H. influenzae and Moraxella destroy amoxicillin, which is why co-amoxiclav (with the β-lactamase inhibitor clavulanate) is used when they are likely. Extended-spectrum β-lactamases in enteric bacteria defeat most cephalosporins and need a carbapenem.
• Altered target. The pneumococcus resists penicillin by altering its penicillin-binding proteins, which a higher dose of amoxicillin can overcome in pneumonia (not in meningitis); MRSA makes an altered binding protein (PBP2a) that defeats all the usual β-lactams.
• Efflux and target modification. Pneumococci resist macrolides by methylating the ribosome or pumping the drug out, so macrolide resistance limits their use as sole treatment.
• Not enough drug. A sequestered focus such as an empyema or abscess, a wrong dose, poor absorption or non-adherence.

03Clinical features

Judging severity

European and British practice uses the CRB65 and CURB65 scores with judgement. The American criteria define severe CAP, which needs intensive care, by one major or three minor criteria:

Judging response

Most patients start to improve in 48 to 72 hours: the fever eases, the pulse and breathing rate fall, and the oxygen need drops. Clinical stability, which allows the switch to oral antibiotics and discharge, means, in the stricter American definition, a fever-free patient with a systolic pressure of 90 mmHg or more, a pulse of 100 or less, a respiratory rate of 24 or less and a saturation of 90 per cent or more on air (or the patient's baseline); the UK rules for stopping antibiotics and for discharge are below. The chest film is slow, and can be worse after improvement; the cough can last for weeks.

A patient who does not improve should be reassessed. The causes of a slowly resolving pneumonia are:

• incorrect or incomplete treatment: resistance, inadequate dose or duration, non-adherence or malabsorption;
• a complication: parapneumonic effusion, empyema or lung abscess;
• an underlying lesion: an obstructing tumour, bronchiectasis or tuberculosis; and
• another diagnosis: pulmonary embolism, cryptogenic organising pneumonia, eosinophilic pneumonia, pulmonary haemorrhage or a lung cancer.

A non-bacterial cause such as influenza should be considered too, a sputum sample sent if not done, and the patient referred to hospital if they fail to improve in the community.

04Diagnosis and management

Supportive care

• Oxygen to a saturation of 94 to 98 per cent (88 to 92 per cent in those at risk of hypercapnia). For respiratory failure that does not respond to a mask, a trial of high-flow nasal oxygen is advised, and some patients benefit from CPAP or non-invasive ventilation.
• Fluids for the dry or hypotensive, with the sepsis pathway when sepsis is suspected.
• Analgesia for pleuritic pain, so that the patient can breathe deeply and cough.
• Thromboprophylaxis with low-molecular-weight heparin for patients admitted for more than 12 hours.
• Nutrition, and physiotherapy only when sputum is retained.
• Stopping smoking, and advice on vaccination.

Antibiotics for adults with community-acquired pneumonia

The usual UK regimens for adults:

Other guidelines differ in detail. American practice gives outpatients without comorbidity amoxicillin 1 g three times a day or doxycycline; hospital patients with non-severe disease a β-lactam with a macrolide, or a fluoroquinolone alone; and severe disease a β-lactam with a macrolide (or a fluoroquinolone). European guidance for severe CAP adds a macrolide, not a fluoroquinolone, to the β-lactam, for 3 to 5 days. In severe disease with penicillin allergy the UK regimen offers levofloxacin only, while other British guidance offers a cephalosporin with clarithromycin where the allergy allows, the non-fluoroquinolone route.

How the antibiotic is used:

• Time. The first dose goes in as soon as the diagnosis is made and within 4 hours of arrival in hospital, and within an hour for patients with high-risk features or suspected sepsis.
• Route. Oral first if the patient can swallow and is not severely ill. If an intravenous drug is started, review by 48 hours and switch to oral to finish the course.
• Duration. Stop after 5 days unless the microbiology calls for longer or the patient is not clinically stable (a fever in the last 48 hours, or more than one of a systolic pressure below 90 mmHg, a pulse over 100, a respiratory rate over 24, a saturation under 90 per cent on air). Longer courses are for complications: an empyema, an abscess, Staph. aureus, or some atypical infections.
• De-escalation. If cultures or the pneumococcal urinary antigen identify the organism, narrow the antibiotic.
• Biomarkers. In hospital, CRP or procalcitonin can be measured on day 3 or 4 if treatment failure is a worry; a high or unchanged level suggests failure and needs a senior review.

Once the cause is known:

The hospital-acquired and immunocompromised regimens are in hospital-acquired pneumonia.

Fluoroquinolones, levofloxacin and moxifloxacin, work against the pneumococcus and the atypical organisms but can cause tendon rupture, neuropathy, psychiatric and sleep disturbance, QT prolongation, aortic dissection and Clostridioides difficile infection. In the UK they are restricted to when other antibiotics are inappropriate, and are not given with a corticosteroid if it can be avoided.

Corticosteroids

Adults with high-severity CAP in hospital can be given a corticosteroid, for 4 to 7 days or until discharge, preferably intravenous hydrocortisone. In a French trial of adults in intensive care, hydrocortisone as an infusion of 200 mg a day, for 4 or 7 days and tapered to 8 or 14 days in all, lowered the 28-day mortality (6.2 against 11.9 per cent); patients on vasopressors for septic shock and with influenza were excluded. Other trials were less clear, and one large trial was stopped early without a large mortality benefit. The older European guidance limits steroids to patients in shock and excludes viral pneumonia, and American guidance moved from advising against routine steroids to suggesting them in severe CAP. A penicillin-allergic patient with high-severity disease is a steroid candidate who is also offered levofloxacin, and a fluoroquinolone is best not given together with a corticosteroid, which favours the non-fluoroquinolone regimen.

Complications and drainage

An effusion is aspirated under ultrasound, and pleural fluid with a pH below 7.2, or frank pus or organisms, means an infected (complicated) effusion or an empyema that must be drained urgently, with a longer antibiotic course. A lung abscess needs a long course, 4 to 6 weeks, and drainage if it does not settle.

05Epidemiology

Pneumonia is one of the commonest reasons for prescribing antibiotics, so how we treat it drives resistance. Pneumococcal resistance to penicillin and to macrolides varies widely between countries, and macrolide resistance tends to be higher in southern than in northern Europe (an EU/EEA mean of 19.0 per cent of invasive isolates in 2024, up from 16.8 per cent in 2020), which is why local data matter and why a macrolide is not used alone as empirical treatment of pneumococcal disease where resistance is common (American guidance allows a macrolide alone only where pneumococcal resistance is below 25 per cent). Mycoplasma resistance to macrolides is very high in East Asia. MRSA, extended-spectrum β-lactamase producers and carbapenem-resistant organisms are the problems of hospital-acquired disease. The consequences for practice are the short 5-day course, the narrowest drug that fits, and the habit of reviewing the antibiotic when the cultures are back; the restrictions on fluoroquinolones follow from their harms.

Short courses are justified by trials and reviews, which found that about 5 days is as good as longer courses in adults who have reached clinical stability, and both American and UK guidance now give 5 days.

06Prognosis

With the right antibiotic, most patients with low- and moderate-severity pneumonia recover in a few weeks. Patients can be given a timetable: the fever is gone in a week; by 4 weeks the chest pain and sputum have gone down; by 6 weeks the cough and breathlessness have; by 3 months most symptoms have gone, although fatigue may linger; and by 6 months most people feel back to normal. Advise them to seek help if the symptoms get worse rapidly, if they do not begin to improve within 3 days, or if they become systemically unwell.

Discharge and after:

• Do not discharge patients who in the last 24 hours had two or more of a temperature above 37.5 °C, a respiratory rate of 24 or more, a pulse above 100, a systolic pressure of 90 or less, a saturation below 90 per cent, an abnormal mental state, or an inability to eat unaided.
• A follow-up chest film is not routine. Consider one at 6 weeks for patients at risk of lung cancer or lung disease (smokers, over 50), with persisting or worsening symptoms, or unexplained weight loss.
• Prevent the next episode by stopping smoking, by influenza vaccination for those at risk, and by pneumococcal vaccination, given before discharge to unvaccinated patients over 65 admitted with CAP. COVID-19 and RSV vaccination are offered to the groups at risk.