Legionella-associated lung abscess : Critical pathogen or minor isolate ?

Two cases of lung abscess, in which Legionella species were identified in association with other bacterial isolates, are presented. In the first case, Legionella pneumophila and Klebsiella pneumoniae were identified in a 24-year-old post renal transplant patient with a right upper lobe pulmonary abscess. Healing did not occur until the institution of specific therapy directed against legionella. In the second case, Legionella micdadei and several other respiratory bacterial pathogens were identified in a 74-year-old woman with a lung abscess. The patient later died with multisystem failure despite adequate antimicrobial therapy. Prior cases of legionella-associated lung abscess have occurred predominantly in corticosteroid-treated patients. The role of coexisting bacterial isolates remains obscure.

L EGIONELLA PNEUMOPI-l/LA AND LEGIONELLA MICDADEI ARE the most common human pathogens within the family Legionellaceae.Both organisms typically cause pneumonia: each also is capable of a self-limited nonpneumonic febrile illness (Pontiac fever and Lochgoilhead fever , respectively).Pneumon ia can occur with coinfection by both agents (1).Abscess formation is a rare complication of leO'ionellosis.1\vo cases in which pulmonary cavitation was a major clin ical presentation oflegionella infection are reported.The incidence ofthis under-recognized complication of legionellosis is reviewed.and its diagnostic and therapeutic implications are discussed.

CASE PRESENTATIONS Case 1:
A 24-year-old male, who had been a renal transplant recipient four years previously.presented with three-week history of fever and cough .He had a past medical history of asU1111a and alcohol abuse.and smoked 10 cigarettes per day.Medications were cyclosporine 90 mg twice daily and predni one 20 mg on alternate clays.On examination he was in no distress: the respiratory rate was 22/min with generalized expiratory wheezing.Chest x -ray showed a 1ight upper lobe cavity (Figure 1) .Bronchoalveolar lavage fluid .obtained from this lobe at bronchoscopy.grew Klebsiella pneumoniae.Anaerobes were not isolated.Monoclonal direct fluorescent antibody specific for L pneumophila (Genetic Systems.Washington) showed positive staining on this specimen.but the organism was not cultured.The patient responded to a two-week course of e1yU1romycin 500 mg intravenously four times daily.but relapsed while taking oral ciprofloxacin 500 mg twice daily as an outpatient.Ciprofloxacin was continued with the addition of erythromycin and rifampin with complete resolution of the abscess cavity.Case 2: A 74-year-old woman was admitted wiU1 a on e-week history of fever.malaise.cough and myalgia.and a one-day history of dyspnea.Past medical history was positive for hypertension.ischemic heart disease and transient ischemic attacks.There was no history of tuberculosis, recent travel or smoking.Medications included diuretics and amoxicillin for the previous day.The patient had a temperature of 38°C and a respiratory rate of 44/min.Mild neck stiffness and delirium were noted.There was bronchial breathing at the left base and ch est x-ray demonstrated lingular consolidation.Arterial blood gases obtained on room air sh owed: pH 7.41: PC02 26 mmHg; P02 52 mm of bicarbonate, 17 mmol/L.The patient was hyponatremic and in renal failure (serum creatinine 324 pmol/L) .Fibrotic bronchoscopy was performed; bronchoalveolar lavage fluid grew L micdadei.Staphylococcus aureus.Haemophilus influenzae , group G streptococci and coliforms .Anaerobes were not isolated .Treatment with erythromycin 500 mg, cloxacillin 1 0' and ampicillin 1 g. each every 6 h. was given intravenously.The patient required mechanical ventilation late on the day of admiss ion and by the fifth hospital day.an extensive cavity was noted in the lingula (Figure 2) .The patient later developed an uric renal failure, and peripheral gangrene of the toes and fingers.She died on clay 12.

DISCUSSION
Lung abscess is an uncommon complication of L pneumophila pneumonia.While this disease has an estimated incidence of 12 cases per 100.000 per year.only 40 cases of abscess formation have been described (2 -12).
The first patient represents a probable case of L pneumophila pneumonia with ab cess formation.Although the organism was not cultured.L pneumophila antigen was detected.The monoclonal immunofluorescent antibody used to identify L pneumophila has been shown to have weal< cross-reactivity only to Staph aureus and occasional LactobaciLLus species .Neither species was cu ltured from this patient.Culture-negative, direct fluorescent antibody-positive cases were present. in some of the cases reviewed (in which the diagnosis was confirmed serologically).The presence of legionella in the patient was supported further by a rapid clinical response to erythromycin alone dUiing initial therapy.and by subsequent relapse while receiving an agent that would have been active aO'ainst K pneumoniae .
This post renal transplant patient was a lso typical of most reported cases of legionella-associated lung abscess. in which 90% (37 of 40) were immunocom-promised.Most patients were being treated with corticosteroids when lung abscess was diagnosed (33 of 44, 80%).Although cytotoxic immunosuppressive agents may also be present, they have not been implicated as a risk factor when used in isolation.Legionellae are facultative intracellular pathogens, and likely it is corticosteroid-induced impairment of cell -mediated immunity, particularly monocyte-lymphocyte function, which incr eases host susceptibility to thes e organisms (11) .Senecal and co-workers (5) h ave shown that these patients are characterized by nosocomial acquisition of pneumonia (73%), prior solid organ transplantation (44%).rapid progression to abscess formation over one to two weeks, slow radiological evidence of h ealing and a high mortality rate (30%).These patients fail to show the usual older age distribution and male predominance of most groups who acquire legionel!osis.reflecting the importance of depressed in1m unity as a key risk factor.
L micdadei is an uncommon cause of pneumonia but has a greater propensity to cause abscess formation .Of the 104 evaluable cases of L micdadei pneumonia which have been reported since 1977.11 cases (10.5%) of pulmonary cavitation have been documented previously (13).Ten of these pa tients acquired pneumonia while in hospital and were being treated with corticosteroids before its a dvent.The second case reported here is unusual in that L micdadei was associated with abscess fo rmation in a host who n either had nosocomial pneumonia nor was obviously immunocompromised except for h er age.One prior case of L micdadei pneumonia has been reported where a bscess form ation occurred in the a bsence of corticosteroid use (14) .
Macroscopic abscess formation at autopsy was not always evident radiologically in the 51 cases reviewed.suggesting that the overall incidence of pulmonary cavitation in legionellosis may be underes timated.This same incidence probably is overestimated by a utopsy studies, which may select for a population more likely to have lung abscess.One such study (15) demonstrated abscess formation in 24% (10 of 42) of patients with L pneumophila and 55% (five of nine) of those with Lmicdadei.
The role of legionella in pulmonary cavitation has been obscured by the presence of other pathogens or by the fail ure to describe microbiologic investigations more completely .Analysis of the 40 cases previously described demonstrated L pneumophila as th e sole isolate in 14 (35%).These cases used culture techniques aimed at recovery of anaerobic, fungal and mycobacterial paU1ogens .In another seven cases (17%), oU1er pathogenic bacteria were recovered .while incomplete data were available for th e remaining 19 cases (48%).It is possible th at bacterial copathogens played a dominant role in th ose cases in which they were identified.Broad spectrum antibiotics .used before the iso lation of legionella.also may have eradicated other bacterial

Figure 2b) Antero-posterior view of the chest radiograph of patient 2 obtained on the 12th hospita l day showing conso lida• lion and abscess fom1ation w ithin the lingula (aTTow). bilateral a lveo lar infiltrates and extensive arterial calcifl.catio n
copathogens in cases where only legionella was isola ted.However.there is strong evidence that legionella as a sole pathogen may cause pulmonmy cavitation .lt has been isolated in pure culture by invasive techniques (eg, open lung biopsy or percutaneous lung asp ira tion) in cases in which the dura tion of previous antibiotic therapy would be unlikely to have eliminated o U1er co pathogens.In many cases , patients continued to deteriorate on antibiotic regimens a dequate for most bacteria l pathogens.while recovery occurred only with the a ddition of erythromycin.Survival has been associated wiili u se of erythromycin.while in nonsurvivors, its u se was either withheld, delayed or inadequate (5).On the other hand.investigations for Legionella species may be delayed because of the presence of other bacterial pathogens.leading to unn ecessary morbidity and mortali ty.
In cases in which isolation of legionella are associated with a polymicrobial infection.each bactet-ial species m ay contribute to the pathogenesis of lu ng a bscess.A symbiotic re lationship m ay exist be tween legionell a and other copathogens .as h as been demonstrated b etween L pneumophila and H injlue11Zae (16).
Lung abscess has been viewed traditionally as a polymicrobial infection .often with a high incid en ce of a n aerobes .occurring in pa tien ts at hig h ris k of asp iration (17).However.legionella-associated lung abscess often occurs in patient as a s in gle pathogen: a nae robes are rarely isolated a nd as piration has not been s hown as the principal mod e of transmission.Is Iegionella lung abscess a uniqu e e nti ty? Proba bly not.as recent data suggest that 50% of lung abscesses can be monomicrobial.and less than one-half of monomicrobial cases contained anaerobic pathogens (18).The microbiology of lung a bscess varies with th e patient population.Nosocomially acq uired lung a bscess in immunocompromised hosts has nol bee n we ll -studie d as a n isolated g roup .Th e above findin gs may be more typical o f the e patients.
Muder (19) h a offered a convincing a rgum e nt imp li catin g asp iration as a mode of tra nsmission in legionellosis.However.a bscess formation in legionellos is does not a lways occu r in the u sual s ites typ ical for

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as piration pne umonia and appear s to have a d iffer en t a natomic distribution from typ ical legione lla pneumonia (in which the re is predominant lower lobe involvem ent).Aspiration cannot be con ide red a proven m echanism in either s ituation thus far.Legionella infection should be pursu ed as a cause of lung a bscess in those patients with unde rlying immunodeficie ncy.p a rticularly if they are receiving cortico t roids or fa il.ing to respond to conventional treatmenl.Since it is ra re .it probably does not n eed to be strongly considered in other circ umstances of pulmonary cavitation.Optimal U1erapy is unknown .but most patients require e tythromycin.4 g daily in travenous ly. for a minimum of three weeks o r until a n adequate c linical response is achieved.followed by a co urse of oral e tythromycin .Rifampin has been a dvocated for its potentia l synergistic effect.but repo rts of its a dded be n e fit in lung abscess so far are only anecdotal.

CONCLUSIONS
In su mmary.evidence implicatinO" L p neumophila and L micdadei as s ignificant pathogens in pulmonary a bscess formation in immunocompromised patients has been presented.A literatu re review s uggests that this complication m ay occur with greater frequency with L micdadei.While the contribution of other bacterial s pecies.whe n isolated.r em a ins unlmown in legionellaassociated lung abscess.their presen ce shou ld n ot obviate a search for coexistin O" Legionella species in U1e immunosuppressed h ost.

Figure 1 )
Figure 1) Postero-anterior uiew of the chest radiograph of patient 1 performed on admission to hospital.Note the well -c ircumscribed radioluscent cauity located in I he apex of the right upper lobe.A prior chest radiogmph was nom1al Figure 2a) Computed tomographic scan of the chest of patient 2 obtained on the seventh hospital day showing an abscess cavity (aTTow) with an area of lingular consolidation and large bilateral pleural effusions