Thorax (1960), 15, 82.

PULMONARY MANIFESTATIONS OF STAPHYLOCOCCALPYAEMIA

BY

D. R. HAYFroml Christcliurch Hospital, Christchurcli, New Zealand

(RECEIVED FOR PUBLICATION SEPTEMBER 30, 1959)

In a previous study (Hay, 1960), the incidenceof staphylococcal septicaemia and pyaemia at theChristchurch Hospital was shown to have risenconsiderably in recent years. The patientspresented in a variety of ways, and frequentlypulmonary signs or a chest radiograph gave theclue to the diagnosis. The object of this paper isto review the natural history of staphylococcalpyaemia as it affects the lungs (hereafter calledstaphylococcal pyaemic pulmonary disease).

PATIENTS STUDIEDSeventy-one patients in the years 1957 and 1958

were proved by blood culture or necropsy to havestaphylococcal septicaemia or pyaemia. Thirty-one of these were judged to have pulmonary com-plications, and, together with two other patientsseen during January, 1959, form the basis ofthis study. The criteria for inclusion in thepulmonary group were radiological abnormalitiesappearing during the acute illness, or signs ofmetastatic suppurative infarcts in the lungs atnecropsy.The diagnosis of staphylococcal septicaemia

was suspected during life in 29 of the 33 patients,and confirmed by blood cultures in 23 of these. Inthe remainder the diagnosis was confirmed atnecropsy. Pyaemic pulmonary complicationswere suspected or confirmed during life in 26patients; the seven other cases were revealed bynecropsy.

AGE AND SEX INCIDENCE AND MORTALITY.-The33 patients included 20 men and 13 women.Their ages ranged from 2 days to 79 years, witha mean of 27 years. Fifteen patients (45%) died.UNDERLYING DISEASES.-The diseases under-

lying the staphylococcal septicaemia were thefollowing:

Post-operative septicaemia ... 9 patientsInfections of the head and neck ... 9 ,,Osteomyelitis and suppurative arthritis 9Umbilical infections 3

Miscellaneous infections ... 6

CLINICAL FEATURES OF STAPHYLOCOCCAL PYAEMICPULMONARY DISEASE

This analysis of symptoms and signs is based onthe findings in the 26 patients with staphylococcalpyaemic pulmonary disease diagnosed during life.PRESENTING SYMPTOMS.-Chest pain was the

most frequent symptom and occurred in 12 outof 21 patients over the age of 5 years. The painwas usually pleural in character, but was associatedwith a friction rub in only four instances. It wasnever of marked severity and lasted one to threedays. Cough occurred in six patients and wasthus infrequent as a presenting or late symptom.Only three patients produced purulent sputum atthe time of diagnosis; one patient coughed upblood-stained sputum, and five complained ofdyspnoea.PRESENTING PULMONARY PHYSICAL SIGNS.-The

most frequent presenting physical signs ofstaphylococcal pyaemic pulmonary disease arelisted in Table I. Physical signs were present in

TABLE IPRESENTING PULMONARY SIGNS IN 26 PATIENTS WITHSTAPHYLOCOCCAL PYAEMIC PULMONARY DISEASE

DIAGNOSED DURING LIFE

Pulmonary Signs No. of Cases

Scattered rales in one or both lungs 8Increased respiratory rate .. 11Consolidation .. . 6Pleural frictionrub. . 4Shock... 3Pneumothorax IPleural fluid .. 2No physical signs...5

most patients, but they were never gross andconsisted usually of an increase in the respiratoryrate or an alteratioh in the character of breathing,together with scattered moist sounds in one orboth lungs. Obvious consolidation with bronchialbreathing was unusual, and pleural friction wasmuch less frequent than pleural pain. The initialradiological changes were usually inconspicuous,and this is reflected in the paucity of physical

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signs. Three patients showed signs of shock,together with fever and respiratory distress.These included two post-operative patients, oneof whom also had an A-V nodal tachycardia, anda woman with an overwhelming infection whichwas believed to arise from the pelvis.

LATER PULMONARY SYMPTOMS AND SIGNs.-Fewof the patients developed outstanding pulmonarysymptoms, and widespread radiological changeswere often present without cough or sputum, andwith only minor pulmonary physical signs.Adventitious sounds occurred frequently and wereoften bilateral, and disappeared after seven to 10days. The most striking symptoms and signsdeveloped when a pneumothorax complicated theillness. This occurred in four patients, two ofwhom were infants with fatal umbilical infection.The third patient (Case 31) had osteomyelitisof the clavicle and showed signs of bilateralconsolidation on admission. A tension pneumo-thorax developed on the right side on the thirdday, and two days later a pneumothorax occurredon the left side. After a stormy illness he slowlyrecovered, but it was not until weeks later, whena pathological fracture appeared in the rightclavicle, that the original site of the staphylococcalinfection was revealed. The pneumothorax inthe fourth patient (Case 72) was revealed by aroutine radiograph taken 21 days after the onsetof pulmonary disease. He had not complained ofdyspnoea but had physical signs of a pneumo-thorax. In both the previous patients, thepneumothorax occurred first in the lung showingthe smaller amount of pulmonary consolidation;both patients recovered well with intercostaldrainage.

It was not uncommon for a trace of fluid tobe demonstrated radiologically in one or bothpleurae. This occurred in 11 patients, in five ofwhom the fluid was bilateral, but in only two wasthere sufficient to be obvious or significantclinically. Empyema occurred once only, in aninfant with fatal parotitis and facial infection.There were few patients who produced sputum,

and haemoptysis never occurred as a latesymptom. The change from solid pulmonarylesions to small cavities was not accompanied bya productive cough.The symptoms and signs of the underlying

primary staphylococcal illness often dominatedthe clinical picture, and identification of thecausative organism was readily possible fromculture of various purulent discharges. Thedetails of the primary illnesses will not be furtherconsidered in this paper.

RADIOLOGICAL SIGNS OF STAPHYLOCOCCALPYAEMIC PULMONARY DISEASE

RELATION OF RADIOLOGICAL ABNORMALITIES TOTIME OF POSITIVE BLOOD CULTURE.-In 16 of the23 patients with positive blood cultures, the firstchest radiograph taken was abnormal. In eightthe abnormality was present before the bloodculture was taken, the diagnosis of staphylococcalpyaemia being suggested by the radiograph. Theother eight patients all had radiographicabnormalities on the same day as the positiveblood culture. In five other patients a radiographwas taken within a week of the positive cultureand found to be abnormal.

In one patient the radiograph on the day ofthe positive blood culture was normal, but patchyconsolidation in the left lower lobe was demon-strated in a radiograph two weeks later.

Another infant in whom the diagnosis was notconfirmed by blood culture had a normal radio-graph one day, followed by a spontaneouspneumothorax the next. Another child of 8 (Case39) had a normal radiograph two days after apositive blood culture, but at necropsy five dayslater there were scattered small metastaticpulmonary abscesses. In two other patients,normal chest radiographs were reported after thediagnosis of staphylococcal pyaemia had beenmade, but necropsy revealed pulmonary lesions.One was a woman of 62 years (Case 41) withsuppurative arthritis of the shoulder, who had anormal radiograph seven days after a positiveblood culture, but was shown to have a largeseptic infarct in the right middle lobe at necropsya week later.EARLY RADIOLOGICAL SIGNS. - The earliest

radiological signs of staphylococcal pyaemicpulmonary disease consist of oval or round, lowdensity shadows situated peripherally, usually inthe middle zone of the lungs. The diameter ofthe opacities may range from 0.5 to 1.5 cm., andonly one may be visible in the first radiograph.Interpretation may be difficult when such solitarylesions are present, but almost invariably secondfilms taken within one to four days will revealfurther lesions or a slight increase in the size ofthe shadows. In the presence of a historysuggestive of staphylococcal septicaemia, theseminor lesions are most significant and may pointto the correct diagnosis. This is well illustratedby Case 71 in which the original diagnosis wasrheumatic fever. An urgent chest radiographshowed a 1 cm. opacity in the left middle zonewhich increased in size within 48 hours, when

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FIG. I.-Case No. 71: Close-up view of the left mid-zone to showearly pyaemic lung lesions in a patient with acute osteomyelitis.

FIG. 2.-Case No. 71: A radiograph 48 hours after that of Fig. 1,showing scattered, ill-defined pyaemic lesions in both lungs.

FIG. 3.-Case No. 27: Early pyaemic lesions in the right and leftmid-zones in the admission radiograph of a boy with fulminatingosteomyelitis.

other shadows had also appeared (Figs. 1 and 2).Subsequently he developed a pneumothorax.Another boy, who died from fulminating infectionarising from osteomyelitis (Case 27), also showedunimpressive small bilateral opacities in theradiograph taken on admission, but within 24hours the extent of consolidation had increasedconsiderably (Figs. 3 and 4).

Pleural effusion was rarely seen as an earlysign, and on only two occasions was a pneumo-thorax present within two days of diagnosis.LATER RADIOLOGICAL SIGNS.-In 11 surviving

patients whose early radiographs showed typicalpyaemic lesions, frequent subsequent films were

FIG. 4.-Case No. 27: The same patient as in Fig. 3, showingincreased pulmonary consolidation within 24 hours.

taken in order to follow the natural history of thiscomplication of staphylococcal infection. Thepulmonary consolidation was most marked on thefirst radiograph in four patients, but in theremainder the most advanced consolidation wasnot evident until the fifth day. In all patientstreatment with appropriate antibiotics had beeninstituted from the time of the earliest radiographor before.The size of the pyaemic infarcts was variable,

averaging about 1.5 by 1.0 cm. but at times aslarge as 4.5 by 6.0 cm. Progression of thepulmonary disease was more often revealed bythe appearance of new lesions than by the increase

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FIG. 5.-Case No. 63: Very extensive bilateral consolidation in apatient with fulminating staphylococcal pyaemia.

in size of existing ones. In occasional patients,the infarcts were more confluent, as in Case 63of which the radiograph is illustrated in Fig. 5.At necropsy, the suppurative foci were shown tobe based around blood vessels containing septicthrombi, which appeared to have come from anarea of suppurative thrombophlebitis in thepelvis.

In nine of the 11 patients under analysis and intwo others of the series, the development of small" cavities " or cysts was noted. These were roundor oval, thin-walled, air-containing lesions, about1.5 to 1 cm. in diameter, situated at the peripheryof the lung, in close relation to the pyaemicinfarcts. Fluid levels were rarely seen andultimately these " ring shadows " disappearedwith almost no residual abnormality. In twopatients, the cavities were present in the firstradiograph, but for the remainder the averagetime of appearance was on the seventh day.More than one was usually present at a time andsometimes as many as six. Typical examples areshown in Figs. 6 and 7.These lesions are thought not to be necrotic

cavities, but to develop as the result of regionalobstructive emphysema secondary to the acuteinflammatory process around the pyaemicinfarcts. Sometimes the small cysts may coalesceto form large bullae, and either small or largelesions may rupture and cause a pneumothorax.This complication occurred in two patients of thegroup, and is illustrated in Fig. 8.

Pleural effusion developed later in 11 patients,but was usually only a trace at the costophrenicangle, except in two instances when the quantity

FIG. 6.-Case No. 48: Close-up view of a typical " cavity " or cystin the left upper lobe.

:R: .a .. ...:: .R..>

FIG. 7.-Case No. 47: Thin-walled " cavity " in the left upper lobeof a patient with pyaemia following a facial boil.

was moderate. Small bilateral effusions occurredin five patients.Ten patients with staphylococcal pyaemic

pulmonary disease, reviewed later, have shownalmost normal chest radiographs two to threemonths after the acute illness. Further examplesof the radiological abnormalities are shown inFigs. 9 and 10.

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IF110. 8.-Case No. 71: A large bulla in the right mid-zone, and a

pneumothorax with adhesions on the same side. Small cystsare also present in the left mid-zone.

FIG. 10.-Case No. 40: The same patient as in Fig. 9 showingconsiderable resolution within two weeks. A subsequentradiograph showed no residual abnormality.

Fti. 9.-Case No. 40: Scattered pyaemic infarcts in the periphery ofboth lungs in a patient with pyaemia secondarv to facial infection.There is a trace of fluid in both pleural cavities.

BACTERIOLOGYAs most patients produced no sputum. it was

difficult to obtain specimens for bacteriologicalexamination. Sputa from 12 patients wereexamined and nine grew staphylococci, the anti-biotic sensitivities of which paralleled the resultsfrom blood cultures. In 10 other patients. swabstaken from the lung at necropsy grew staphylo-cocci which were penicillin-resistant in eightinstances. Of the 33 patients in the pulmonaryseries, only six (18%) were infected by penicillin-sensitive staphylococci. This is somewhat lowerthan the figure of 28 O0, for the larger series ofstaphylococcal septicaemia (Hay, 1960). However.it would be unjustified to infer from this figurethat infections by penicillin-resistant organismswere more likely to be complicated by pyaemicpulnmonary disease.

PATHOLOGY

Necropsies were performed in all 15 fatalcases. A fibrinous exudate was frequentlypresent on the pleural surface of the lungs, withsmall effusions in several cases but an empyema inonly one. The metastatic abscesses were usuallyvisible to the naked eye and were characteristic-

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PULMONARY MANIFESTATIONS OF STAPHYLOCOCCAL PYAEMIA

ally subpleural in situation and unrelated to majorbronchi. In the early stages, these lesionsconsisted of discrete areas of haemorrhagicconsolidation, the centre of which later becamenecrotic and pale and finally obviously purulent.Small air-filled cysts in relation to the abscesseswere noted in several patients, but never werethere large chronic abscesses. On microscopicexamination, the foci of inflammation andsuppuration were shown to be related to bloodvessels and septic clot was frequently demon-strated in both arteries and veins. Colonies ofdarkly-staining staphylococci were obvious in thesections.

TREATMENTThe antibiotic treatment of the patients in this

study has been discussed elsewhere. Drugs whichwere considered appropriate from the results ofsensitivity tests in vitro were given in high dosageand continued for a month. The response totreatment was related to the nature of the under-lying staphylococcal illness, its duration, and thedelay before diagnosis was made. Three patientsdied within 48 hours of admission, presumablyfrom the effect of overwhelming toxaemia. Thesuccesses in therapy were achieved by prolongedand adequate treatment with penicillin whenindicated or with combinations of erythromycinand novobiocin. Surgical treatment was requiredonly for the management of spontaneous pneumo-thoraces. Postural drainage and other forms ofphysiotherapy were of no value in these patients.

DISCUSSIONThe high incidence of serious staphylococcal

disease has been one of the notable features ofmedical practice at the Christchurch Hospital inthe last three years. Staphylococcal septicaemiamust now enter into the differential diagnosisof any unexplained pyrexia or post-operativecollapse. When there are obvious foci ofstaphylococcal infection, more serious complica-tions are possible and should be excluded byurgent blood cultures.

In the present study 44% of patients withstaphylococcal septicaemia had pulmonarycomplications, and characteristic radiographicchanges were frequent. Chest radiographs aredesirable early, whenever this diagnosis issuspected, and should be repeated within two daysif the first radiograph shows suspicious lesions.The diagnostic value of apparently trivialpulmonary lesions in confirming suspectedstaphylococcal pyaemia was demonstratedrepeatedly, and in a number of patients the

diagnosis was first suggested by the radiologist.Although most patients with staphylococcalpyaemic pulmonary disease showed radiologicalabnormalities at some time, in a few the lesionswere too small to produce a visible opacity. Thusthe incidence of pulmonary miliary abscessesat necropsy exceeded the number demonstratedduring life. The size of the abscesses and thedelay before they became radiologically visible aredoubtless related to the virulence of the organismand the resistance of the host.Pulmonary physical signs were usually present

when metastatic pulmonary complications hadoccurred, but symptoms were less common.Chest pain was the most important, and itsfrequency was related to the subpleural situation ofmany of the pulmonary infarcts. The importantphysical signs were an increased respiratory rateand adventitious sounds in one or both lungs.These abnormalities were often trivial andrequired careful observation for their detection.The prognosis of staphylococcal pyaemic

pulmonary disease is difficult to assess, for it isthe underlying primary staphylococcal infectionwhich often determines the patient's fate. Themortality in this particular group was 45 %, whichis slightly less than the figure of 50 % for thelarger series of patients with staphylococcalsepticaemia (Hay, 1960). In the patients whorecovered, extensive bilateral consolidation oftenresolved completely and the small cavities orcysts which were conspicuous during the acuteillness disappeared entirely. Follow-up broncho-grams were not undertaken, but in view of thenormal radiographs taken after three months itseems unlikely that these patients were left withsignificant structural damage to the lungs. Thisis in contrast to primary staphylococcalpneumonia, which may lead to the developmentof bronchiectatic changes in the affected lungsegments.

Except for the one patient whose radiograph isillustrated in Fig. 5, the pulmonary disease itselfwas probably never the primary cause of death.Pyaemic spread to the lungs always leads to thedanger of pneumothorax, for which carefulclinical and radiological watch must be kept.Empyema, on the other hand, was not aproblem in these patients, which is surprising inview of the nature and situation of the suppura-tive infarcts. Perhaps the antibiotic treatmentprevented this complication, although it did notalways prevent an increase in the extent ofpulmonary consolidation.The frequency of pulmonary involvement in

published accounts of staphylococcal septicaemia

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is difficult to assess, and there is little recentinformation on the subject. Mendell (1939) founda 63% incidence of pulmonary complications in35 patients with staphylococcal septicaemia, whileSkinner and Keefer (1941) observed metastaticrespiratory tract infections in 30% of 122 patients.In a more recent report, Schirger, Martin, andNichols (1957) record only three cases in 109antibiotic-treated patients with staphylococcalbacteraemia, while Hassall and Rountree (1959)make no mention of pulmonary complicationsamong their 86 patients with staphylococcalsepticaemia.

Primary staphylococcal pneumonia orpneumonia complicating influenza or other virusinfections of the respiratory tract is common(Oswald, Shooter, and Curwen, 1958; Robertson,Caley, and Moore, 1958), but this disease shouldbe distinguished from pyaemic staphylococcalinfection of the lungs. The former ischaracterized by lobar or multilobar consolida-tion, and by conspicuous respiratory symptomsand signs. Sputum is usual, empyema iscommon, but positive blood cultures are seldomobserved. In staphylococcal pyaemic pulmonarydisease, the signs of the underlying infectionoften predominate and the respiratory signs maywell be overlooked. The chest radiograph showscharacteristic multiple small opacities, and bloodcultures are almost always positive. Cavitationand pneumothoraces may occur in eithercondition, but persistent structural damage isunusual in pyaemic infection. Successfultreatment demands the use of appropriateantibiotics for periods of three to four weeks inthe case of pyaemic pulmonary disease, but resultsremain somewhat unsatisfactory.

SUMMARY

Thirty-three patients with pulmonary com-plications of staphylococcal pyaemia have beenstudied.

Pulmonary symptoms and signs wereinconspicuous: chest pain was the most commonsymptom, and an increased respiratory rate andscattered moist sounds the most importantphysical signs.The characteristic radiological signs were

multiple, oval, or round opacities situated in theperiphery of both lungs. Thin-walled cavities orcysts developed in 11 patients, but almost completeresolution eventually occurred. Four patientsdeveloped pneumothoraces, and in 11 the'rewere small pleural effusions. Repeated chestradiographs were valuable in assessing suspiciouslesions.Only six patients (18%) were infected by

penicillin-sensitive staphylococci. Staphylococciwere grown from the sputum of nine of the 12patients who produced specimens.

Fifteen patients (45 %) died, but in only one wasthe pulmonary disease the main cause of death.Successful treatment demanded prolonged coursesof antibiotics.The incidence of pulmonary complications was

44% of a series of 71 patients with staphylococcalsepticaemia, a figure higher than in other recentlypublished series.

I wish to thank the physicians and surgeons of theChristchurch Hospital for permission to study theirpatients. I am grateful to Dr. G. L. Rolleston andto my wife, Dr. Jocelyn Hay, for their advice andcriticism, and to Mrs. Margaret Meyer for hersecretarial assistance. The illustrations were preparedby Messrs. K. Donaldson and S. Brooks.

REFERENCESHassall, J. E., and Rountree, P. M. (1959). Lancet, 1, 213.Hay, D. R. (1960). Quart. J. Med. In the press.Mendell, T. H. (1939). Arch. intern. Med., 63, 1068.Oswald, N. C., Shooter, R. A., and Curwen, M. P. (1958). Brit. med.

J., 2, 1305.Robertson, L., Caley, J. P., and Moore, J. (1958). Lancet, 2, 233.Schirger, A., Martin, W. G., and Nichols, D. R. (1957). Ann. intern.

Med., 47, 39.Skinner, D., and Keefer.. C. S. (1941). Arch. intern. Med., 68, 851.

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