Pneumonia - Postgraduate Medical Journal · PNEUMONIA 371 treatment. Isolation oftheorganismfromthesputum isnotusuallypossiblebuttrans-trachealaspiratesmay reveal Legionella. Extensive

Postgraduate Medical Journal (1986) 62, 369-376

Emergency Medicine

Pneumonia

C.G. Wathen and M.F. SudlowDepartments ofMedicine and Respiratory Medicine, Royal Infirmary and City Hospital, Edinburgh EH3 9YW,UK.

Pneumonia is inflammation within the lung caused byinfection with micro-organisms. Clinically the diag-nosis is made either by physical signs or radiologicalevidence of consolidation within the lungs. The termspneumonitis and alveolitis also imply inflammationbut in practice are reserved for conditions associatedwith chemical and physical injury to the lungs.Physical signs to localize abnormalities in the chest arenot very reliable and in practice without good chest X-rays it is difficult to distinguish pneumonia from otherchest infections, particularly in patients with pre-exist-ing lung disease.Pneumonia occurs throughout the world but there is

little comparative data between countries (Bulla &Hitze, 1978). The major bacterial cause ofpneumoniaremains Streptococcuspneumoniae (MacFarlane et al.,1982; British Thoracic Society, 1985) but its incidencehas been declining in the past 30 to 40 years. This hasbeen attributed both to the introduction of penicillinand sulphonamides and improving social conditions(Crofton & Douglas, 1981). The largest decrease inincidence has been in the infant population and the riseseen in the elderly indicates that pneumonia is acommon terminal event at the end of life. The totalnumber ofdeaths in patients under 50 years in the UKis still 3 to 5 times that due to asthma (Charlton et al.,1983). In all ages males have a higher mortality thanfemales. Pneumonia is more common in the wintermonths and also in areas where there is atmosphericpollution.

There is little community based information aboutthe epidemiology of pneumonia using radiologicaltechniques to confirm the presence of pneumonia andmost studies relate to hospital admissions. In Bristol(White et al., 1981) 210 consecutive patients admittedto hospital with a primary diagnosis of pneumoniabetween 1974 and 1980 were studied; pneumonia dueto Mycoplasma pneumoniae was the most common(14% of patients) compared with pneumococcalpneumonia (11.5% patients) and influenza A

pneumonia. In this study however, no pathogen wasdetected in about half of the patients. The highincidence of mycoplasma pneumonia probablyoccurred because of a minor epidemic in Bristol at thetime. In a similar study of 127 patients in Nottingham(MacFarlane et al., 1982) aetiological diagnosis wasobtained in 124 patients. In this study pneumococcalpneumonia accounted for 76% of cases and Legion-naires' disease was the next most common diagnosis,15% of cases. Recently the British Thoracic Societysurvey ofpneumonia has confirmed that St. pneumon-iae and M. pneumoniae are the most common agents(British Thoracic Society, 1985).

Epidemics of viral infection such as respiratorysyncytial virus are associated with increase in theincidence of pneumonia. Communities where in-dividuals live in close contact, such as the long-housedwellers of Papua New Guinea and gold-miners inSouth Africa are particularly prone to epidemics ofpneumonia (Oseasohn et al., 1978).

Pathology and pathophysiology

The micro-organisms enter the lungs through theairways and, depending on the balance between thevirulences and the host's immune state, may multiply.In the case of lobar pneumonia this acts as a stimulusto the immune system and inflammatory reactionoccurs with chemotaxis of cells and the developmentof oedema fluid (Reynolds, 1983). When the hostimmunological defences are reduced, for example dueto cytotoxic chemotherapy or acquired immune de-ficiency syndrome (AIDS), there may be relativelylittle inflammatory reaction, invading pathogens areable to spread, more easily and organisms of lowervirulence may cause active infection.Pneumonia causes hypoxia, hypocapnia and

tachypnoea with respiratory alkalosis. The hypoxiaappears to be due to shunting of venous blood in thelung (Davidson et al., 1972). The cause of the tachyp-noea is not clear and is not solely due to hypoxia. Inanimals, Guz & Trenchard (1971) have shown that a

©D The Fellowship of Postgraduate Medicine, 1986

Correspondence: C.G. Wathen, M.B., Ch.B., M.R.C.P.Accepted: 31 December 1985.

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370 C.G. WATHEN & M.F. SUDLOW

reflex mediated by the vagus nerve from the infectedlung is involved. The tachypnoea produces hypocap-nia and respiratory alkalosis, so the cautious use ofanalgesics with respiratory depressant properties isgenerally not contra-indicated.

Clinical features

The diagnosis oflobar pneumonia is seldom a problemif history has been taken, careful examination carriedout and a chest radiograph obtained. Similarly bron-chopneumonia which is a commoner condition inhospital practice does not usually present a problem indiagnosis, in patients with pre-existing lung diseasesuch as chronic bronchitis. In these patients it must beremembered that a chest infection can oftenprecipitate respiratory failure. In patients who do nothave preceding lung disease bronchopneumonia cansometimes be confused with conditions which alsocause diffuse shadowing of the chest X-ray: in par-ticular the inflammation due to chemical irritants andtoxic gases and aspiration ofliquids or smoke. In thesesituations a history of exposure would be expected.Another differential diagnosis is acute allergicalveolitis, but again history ofexposure to allergen, theappropriate laboratory precipitation tests and spon-taneous improvement on removal from the allergenwill differentiate the conditions. The possibility oftuberculosis must always be borne in mind in a personwho appears to have pneumonia which does notrespond to appropriate drug therapy. It must also beremembered that co-existing lung disease such asbronchial carcinoma or pulmonary infarction mayhave been the precipitating factor in the developmentof chest infection.

Aetiological diagnosis - bacterial pneumonia

Pneumococcal pneumonia

Streptococcus pneumoniae is the commonest bac-terium causing lobar pneumonia in previously healthysubjects and in the presence of pre-existing lungdisease can cause bronchopneumonia. In the elderlythe clinical features of pyrexia, rigor, cough andpleuritic chest pain may be absent (Finkelstein et al.,1983). Diagnosis may be made by Gram stainedspecimen of sputum which shows the characteristicappearance of paired Gram positive cocci. Sputumculture is usually positive in the first 24 hours andblood cultures may be positive in about 30% of cases.Pneumococcal capsular antigen can be detected insputum, blood or urine by countercurrent immuno-electrophoresis (CIE). This is particularly useful inpatients who have already commenced on antibiotics

as it remains positive in these circumstances (Kalin &Lindberg, 1983). Further characterization is possibleand although there are over 80 recognizable antigenictypes of St. pneumoniae only a few types are commonlyseen in clinical disease (types 1, 2, 3, 6 and 7, 14 and19), so prophylactic vaccination is possible (AmericanCollege of Physicians, 1982). Type 14 may be difficultto detect by antibodies currently available for CIE.

Staphylococcal pneumonia

This is most frequently seen after influenza and indebilitated patients. The pneumonia presents as arapidly progressive severe illness with a high mortality(Schwarzman et al., 1971; White et al., 1981) and ischaracterized on chest radiograph by the developmentof small multiple lung abscesses which may developinto thin walled cavities; pneumothorax is a recog-nized complication. Staphylococci are usually seen inthe Gram stain of sputum in large numbers and ifantibiotics have not been given blood cultures may bepositive. Occasionally staphylococcal pneumonia isseen in drug addicts in whom it is caused byhaematogenous spread. The staphylococcus can causea severe pneumonia in infants.

Legionnaires' disease

This is now thought to account for 3-5% of cases ofcommunity acquired pneumonia (Balows & Fraser,1979; Broome & Fraser, 1979; British ThoracicSociety, 1985). In some studies there has been amortality rate of 50% (Hudson, 1979) but this isprobably due to milder cases not being recognized andin the UK mortality is estimated at 10% (Bartlett &Miller, 1981). There are at least six serotypes of L.pneumophilia and other species of Legionella havebeen recognized. Further, different epidemiologicalpatterns of the disease are recognized (Cameron &Phillips, 1980). The first type recognized was theoutbreak seen and well publicized in the United Statesand more recently in Stafford, England (Hoyle et al.,1985). Sporadic cases are also seen in the Nottinghampneumonia survey (McFarlane et al., 1982). Isolatedcases and epidemics in hospitals among immunocom-promised hosts who are particularly susceptible to L.pneumophilia infection also occur.

Infection is characterized by symptoms of sweating,pyrexia, weight loss with cough productive of sputum,with pus cells from which no organism can be isolated.There is often unexplained confusion, microscopichaematuria and investigations reveal consolidation,often bilateral, on the chest radiograph, neutropenia,hyponatraemia and abnormal liver function tests.These features should alert the clinician to the diag-nosis as laboratory confirmation is by serologicaltesting which will not be available in time for initiating


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treatment. Isolation of the organism from the sputumis not usually possible but trans-tracheal aspirates mayreveal Legionella. Extensive consolidation on thechest radiograph, extreme lymphopenia (less than0.8 x 109/l) and plasma creatinine of more than150 JLmol/l are poor prognostic features.Treatment is with supportive measures, including

ventilation if necessary and antibiotics. Erythromycinshould be given wherever Legionnaires's disease issuspected and rifampicin may also be added, par-ticularly when tuberculosis has been excluded. If this isnot possible the rifampicin should be given withisoniazid.

Klebsiella pneumonia

Klebsiellapneumoniae causes severe pneumonia with avery high mortality. It usually presents in olderalcoholic men and tends to affect the upper lobes. Thedisease is commonly bilateral radiographically andintense oedema often compresses the adjacent lung.Necrosis and abscess formation is common. Classical-ly the sputum is jelly like, blood stained and containsGram negative bacilli which can be cultured. Also itshould be noted that K. oxytoca has more recentlybeen implicated as a cause of pneumonia (Power &Calder, 1983).

Pseudomonas species

Pneumonia due to P. aeruginosa is almost entirelyconfined to hospitalized patients with pre-existinglung disease and is characteristically seen in patientswith cystic fibrosis (British Thoracic Society ResearchCommittee, 1985) and people who are receivingmechanical ventilation when it is often very difficult toestablish whether the organism is causing pneumonia.It is commonly isolated from the sputum in patientswho are being treated with broad spectrum antibioticsand clears when the antibiotics are withdrawn. Othertypes ofpseudomonas may occasionally cause disease.

Tuberculosis

The clinical features of this type of pneumonia arerather different with a history or more gradual onset,haemoptysis, fever and night sweats. The sputum isnot usually purulent and there is no peripheralleucocytosis. Radiographic opacities are very variableso it is important to consider the diagnosis. Examina-tion of the direct sputum film and culture for tuber-culosis should be carried out in any patients withpneumonia not responding to treatment. Tuberculosisis more insidious in the immunocompromised patientand atypical mycobacteria which are usually lesssensitive to treatment are sometimes encountered(Fauci, 1984).

Haemophilus influenza

Although H. influenzae is often isolated in the sputumits role in the pathogenesis of pneumonia is stilldebated. It is most commonly seen as the organismisolated from patients with bronchopneumonia as acomplicating factor in chronic bronchitis andemphysema (McHardy et al., 1980). It has beendescribed as a primary pathogen in pneumonia out-breaks in New Guinea (Schan et al., 1984).

Branhamella catarrrhalis

Only recently has this organism been suggested as apathogen in pulmonary infections (MacLeod et al.,1983). The presence of Gram negative diplocci in theGram film of sputum will alert the clinican to thediagnosis which can be confirmed by sputum culture.Many of these organisms produce P-lactamase andtherefore are resistant to penicillin. It is not yet clearwhether pneumonia is caused by this organism inisolation.

Anaerobic organisms

Anaerobic organisms cause pneumonia in patientswith previous lung disease or immune suppression andare commonly found in aspiration pneumonias. This,along with the presence of abscesses and a pungentodour to the sputum often suggests the diagnosiswhich can be achieved by culture oftracheal aspirationor samples from the lungs as organisms are seldomgrown from sputum. An early clue to the nature of theillness may be obtained from viewing the sputumunder ultra-violet light when the anaerobic organismsfluoresce or by gas-liquid chromatography of thesputum.

Non-bacterial pneumonia

The differentiation between bacterial and non-bac-terial pneumonia depends on microbiological diag-nosis but clinically the systemic features such asheadache, pains, mild fever and relatively few res-piratory symptoms suggest a non-bacterial aetiology.Pleural effusion is uncommon and the sputum is rarelypurulent. The chest radiograph is often more floridthan clinical signs might suggest. Typically the peri-pheral leucocyte count is normal and in clinicalpractice the diagnosis is often made when pneumoniahas failed to respond to conventional antibacterialchemotherapy.

Mycoplasma pneumonia

Mycoplasma pneumoniae is a common cause ofpneumonia in young people and has a seasonal


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variation with most cases in the autumn (MacFarlaneet al., 1981; British Thoracic Society, 1985). Outbreaksare commonly seen in close communities; the organ-ism can be isolated from the sputum but is very slow togrow and diagnosis is usually made by paired serumtitre. Cold agglutinins are present in serum of about50% of patients although there are other causes forthis and the test is of little diagnostic value. They maycause clotting of blood on withdrawal. Tetracyclinesor erythromycin are effective antibiotics against thisorganism.

Rickettsial pneumonia

Q fever, caused by Coxiella burnetti develops aftercontact with cows or sheep and is seen in abattoirworkers. This is a self-limiting pneumonic illnessalthough very occasionally endocarditis has beendescribed. Again the diagnosis is made by demonstra-tion of a rising or raised antibody titre.

Chlamydial pneumonia (psittacosis)

This is acquired from birds such as parrots, bud-gerigars and pigeons by the organism Chlamydiapsittaci. Diagnosis is made by complement fixationtests and it is interesting to note that often theWasserman test is falsely positive. The disease issometimes prolonged and may be associated witherythema nodosum and hepatosplenomegaly. It is besttreated with tetracycline for 10-14 days.

Viral pneumonia

Respiratory syncytial virus (RSV) is a common causeof bronchiolitis in young children who present withcough, wheeze, fever, and tends to occur in epidemicsin the winter. The virus is usually identified by fluores-cent antibody techniques in nasal or throat secretionsand can be cultured by standard virological tech-niques. RSV has also been recognized as a cause ofchest infections in the elderly (Morales et al., 1983) andmay develop into pneumonia in immunosuppressedchildren. Cytomegalovirus (CMV) can cause bron-chopneumonia and interstitial pneumonia in patientswith immunosuppression, notably those followingrenal transplantation. Commonly CMV pneumonia isassociated with other infections such as Pneumocystiscarinii or M. tuberculosis. Measles produces apneumonitis and can go on to produce pneumonia butusually pneumonia in this context is due to secondarybacterial infection. Finally, varicella zoster and herpessimplex can produce pneumonia in immunocom-promised patients (Ramsey et al., 1982). With theadvent of effective anti-viral agents, particularly acy-clovir, the diagnosis ofherpes pneumonial has becomemore important.

Fungal and protozoal pneumonia

This type ofpneumonia is confined to the immunosup-pressed patient (Geddes & Ellis, 1985). P. carinii is arecognized problem (Hasleton & Curry, 1982) and isparticularly prominent in patients with acquiredimmune deficiency syndrome (AIDS) accounting for50-80% of pneumonia in these patients (Johnson,1985). To date transbronchial biopsy or open lungbiopsy have been the most effective ways of makingthe diagnosis but in patients with AIDS, P. cariniimaybe found in bronchial secretions or even sputum.Aspergillus fumigatus has also been recognized as acause of necrotizing pneumonia in debilitatedpatients. The pneumonia presents with extensive con-solidation and rapidly cavitates and causes fibrosis.Again diagnosis may be achieved by bronchial lavageor transbronchial biopsy. Amoebiasis can involve thelung, occasionally by haematogenous spread but moreusually by direct spread through the diaphragm fromthe liver. This gives rise to a right basal pneumoniawith a pleural effusion or empyema. Amoebae may befound in sputum or pus but often the diagnosisdepends upon response to specific treatment withmetronidazole.

Techniques for obtaining better specimens for culture

These techniques are designed for use in the severely illpatient, to obtain better samples where contaminationby organisms from the oropharynx prevents isolation(Bartlett, 1981). Trans-tracheal aspiration, direct lungpuncture and bronchoscopy (Cameron & Phillips,1980) all appear to improve the diagnosis considerablyand should be considered in cases where pneumoniafails to respond to treatment and management. Tra-cheal puncture and catheter aspiration is associatedwith some morbidity and the recently described tech-nique of MacFarlane & Ward (1984) is simpler andappears to produce equally good results. Using thistechnique sputum production is encouraged by induc-ing cough with a small inter-tracheal injection ofsaline.

Management

Having diagnosed pneumonia the clinican may susp-ect a specific aetiology but must take steps to confirmthis by collecting specimens for Gram stain, culture ofsputum and blood and, if available, CIE andserological tests. However, treatment usually has to beinstituted before all these results are available.

It is therefore practical to classify pneumonia intotwo categories: (a) those which respond to treatmentand (b) those which do not respond within 48-72


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hours ofcommencing treatment (Cameron & Phillips,1980). The clinical situation and features alreadyoutlined will influence the choice of initial therapy(Table I). In general oral ampicillin or intra-muscularbenzylpenicillin is the drug of first choice whenpneumococcal pneumonia is suspected but co-trimox-azole is an acceptable alternative in patients withallergy to penicillin. At the time of epidemics ormycoplasma pneumonia or if Legionnaires' disease issuspected as a cause or in any patients with a severepneumonia there is a case for adding erythromycinuntil a bacteriological diagnosis is available (Mac-Farlane et al., 1983). Most patients should improvewith this management but in those not responding tothe initial treatment by 48-72 hours, further investiga-tion and assessment will be required. The results ofthebacteriological culture or from the initial studies maybe available, but commonly this is not the case. It maybe necessary to employ one of the newer methods forobtaining specimens as described above and also toconsider the agents which might be causing the diseaseand are not susceptible to the initial treatment. It willalso be necessary to take appropriate serology forlegionella, mycoplasma and appropriate specimens toexclude a diagnosis of tuberculosis. It is alsoimportant to realise that there may be anatomicalproblems such as obstruction of a major bronchus bycarcinoma. Early referral for bronchoscopy is neces-sary if this is suspected. Again the clinical context maygive a clue to the possible aetiology if no laboratoryresults are to hand. Erythromycin is useful in treatingmycoplasma pneumonia and is an appropriate addi-tion to antimicrobial therapy ifnot already prescribed.Supportive measures including the maintenance ofadequate fluid balance and treatment of any res-piratory failure needs close attention. Further,pleuritic pain may need analgesia. For some of theelderly and those with previous chronic lung diseasearterial blood gas tension should be checked in view ofthe possibility of significant respiratory depressionfrom the disease and analgesic drugs. Whilst manypatients can be managed at home, the more severely ill,particularly those with breathlessness, cyanosis, chestpain, pyrexia, dehydration or pre-existing disease,require hospital treatment. In this hospitalized groupbed-rest will be required initially. This increases thepossibility of thrombo-embolic disease and in a highrisk group prophylaxis with sub-cutaneous heparin isadvisable.

Complications

Pleural effusion

These should be aspirated and drained to try to avoidthe development of empyema. If there is any sugges-

tion of associated lung disease or tuberculosis pleuralbiopsy can be carried out at the same time. The fluidshould be analysed in a microbiology laboratory andalso for protein content. A low hydrogen ion concen-tration suggests infection of the fluid and an increasedpossibility of the development of empyema (Light etal., 1980).

Empyema

Development of empyema is suggested by the symp-toms or signs of pleural effusion in connection withpersistent pyrexia and failure ofthe patient's conditionto improve clinically. Drainage through a fine needle isusually not possible due to the viscosity of the pus andmanagement by tube drainage, irrigation or rib resec-tion is required. Ultrasound examination may beuseful to localize the fluid and determine if there is anempyema.

Lung abscess

This is an unusual complication of pneumococcalpneumonia but is commonly seen with klebsiellapneumonia, staphylococcal pneumonia and aspira-tion pneumonia. The clinical features are persistinginfection, fever and cough productive of largeamounts of pus, which may be foul smelling, suggest-ing secondary infection with anaerobic organisms.Haemoptysis can occur and is occasionally verysevere. Rupture of abscess may occasionally lead topyopneumothorax. The appropriate treatment is withantibiotics and postural drainage. In this contextmetronidazole or similar drug should be used withother antibiotics (Table I) even if no anaerobicorganisms can be isolated. Occasionally surgical resec-tion of abscesses is required. Bronchoscopy should becarried out to exclude bronchial carcinoma or aforeign body. The opportunity should be taken to sendanother specimen for microbiological analysis.

Septic complications

These are unusual in patients treated with antibioticsbut occasionally can occur during pneumococcal orstaphylococcal septicaemia. Arthritis, cellulitis andpericarditis are the more unusual manifestations withbrain abscess still sometimes seen.

Circulatory failure is sometimes seen in complica-tions of septicaemia, frequently in the elderly and isassociated with disseminated intravascular coagula-tion (DIC). DIC is also a recognized complication ofLegionnaires' disease and the development of renalfailure should alert the physician to the possibility ofthis condition if it has not been excluded byappropriate serology.


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Table I Initial antibiotic treatment of pneumonia

Clinical situation Suspected organism Antibiotic

1 Healthy person with pneumonia St. pneumoniae Ampicillin or i.m.acquired outside hospital L. pneumophilia penicillin ± erythromycin

2 Pre-existing chronic lung St. pneumoniae Ampicillin (ordisease (chronic bronchitis) H. influenzae co-trimoxazole) or

Erythromycin3 Pneumonia complicating viral S. aureus Ampicillin or i.m.

infection St. pneumonia penicillin± flucloxacillin

4 Aspiration pneumonia Anaerobic bacteria Ampicillin orGram-negative bacteria tobramycin with

metronidazole5 Immuno-compromised Most organisms e.g. Initially ticarcillin

patients St. pneumoniae (or parenteral cephalosporin)S. aureus + aminoglycosideKlebsiella + metronidazolePseudomonasAnaerobesTuberculosisNon-bacterial infection

Chronic suppurative pneumonia

This is a term used to describe continued fever, chestsigns on clinical examination, purulent sputum,progressive fibrosis and shrinking of the lung onsequential radiographs (Crofton & Douglas, 1981).Usually no organisms are cultured. The condition issometimes associated with aspiration and vegetablematter may be seen in the lung after resection.Resection is indicated ifprolonged chemotherapy failsto cure the illness and this should be carried out underantibiotic cover including metronidazole or similaranti-anaerobic drug. A similar condition termedchronic destructive pneumonia has been described inSouth Africa (Cameron et al., 1980).

Recurrent pneumonia

Recurrence of pneumonia should lead the clinician toreconsider the diagnosis. Pulmonary infarction, ex-acerbations ofbronchiectasis and allergic bronchopul-monary aspergillosis may present with similarradiographic appearances. If a genuine recurrentpneumonia does occur, aspiration from pharyngealpouch, achalasia or other upper gastrointestinal disor-der should be considered. If pneumonia recurs at thesame anatomical site bronchiectasis and underlyingneoplasma or bronchial adenoma should be con-sidered and investigated by bronchoscopy and orbronchography. Rarely, an underlying susceptibilitydue to infections due to hypogammaglobulinaemia,chronic lymphatic leukaemia, multiple myeloma orAIDS may be present.

Adult respiratory distress syndrome

This condition ofnon-cardiogenic pulmonary oedemais caused by lung damage from a wide variety ofnoxious stimuli (Stevens & Raffin, 1984). It is arecognized complication of pneumonia and requiresvery aggressive treatment (Petty & Fowler, 1983).Steroid therapy, mechanical ventilation and control ofinfection are required but the mortality remains high(Murray, 1980).

Discussion

Pneumonia remains an important cause of morbidityand mortality from chest disease in Britain. Themajority of cases are caused by a few types ofpathogens, and appropriate antibiotic treatmentshould therefore be commenced at the time of diag-nosis, pending the results of specific microbiologicalinvestigations. The antibiotics chosen should cover themost likely organisms, particularly Streptococcuspneumoniae and during outbreaks of infection Myco-plasma pneumoniae. Broader spectrum antibiotics arerequired in seriously ill patients who require urgenttreatment before the results of any microbiologicalinvestigations are available.An increasing number of patients are seen in

hospital with pneumonia following immunosuppres-sion with high doses of prednisolone, cytotoxic drugsand more recently AIDS (Johnson, 1985). In thesepatients a wide range of causative organisms needs tobe considered and appropriate investigations to deter-mine the organism involved should be initiated earlyand broad spectrum antibiotic cover is required.


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