nosocomial disease: clinical and radiographic...

REVIEW

Nosocomial Legionnaires~ disease: Clinical and

radiographic patterns THOMAS j MARRIE, MD, DAVID HALDANE, MB, GREGORY BEZANSON, PHD

TJ MARRIE, D HALDANE, G BEZANSON. Nosocomial Legionnaires' disease : Clinical and radiographic patterns. Can J Infect Dis 1992;3(5):253·260. From 1981 to 1991. 55 patien ts (33 males. 22 females. mean age 58.6 years) \v:ilh nosocomial Legionnaires· disease were studied. The mortal ity rate was 64%. One-half of the patients developed nosocomial Legionna ires· disease wiU1in three weeks of admission. A surprising clinical feature was U1e low rate of findings of consolidation on physical examination, despite the fact that 52% of patients had lhis finding on chest radiograph. More U1an one-half of patients had pre-existing lung disease. renclerinO" a radiographic diagnosis of pneumonia clue to Legionella pnewnophila impossible in 16% of cases despite microbiological confim1alion. Nineteen per cent of patients who had blood cultures clone had a pathogen olher lhan L pnewnophila isolated. suggesting dual infection in at least some of lhe patients. When lhe clinical and radiographic findings were combined it was notecllhat 40% of patients had one of lhree patterns suggestive of nosocomial LeO"ionnaires· disease: rapidly progressive pneumonia. lobar opacity and multiple peripheral opacities . However. in 60% of patients U1ere were no distinctive features.

Key Words: Legionnaires· disease. Nosocomial

Maladie du legionnaire nosocomiale: modeles cliniques et radiographiques

RESUME: De 1981 a 1991. 55 patients (33 de sexe masculin ct 22 de sexe feminin: moyenne cl'a<1e: 58.6 ans) atleints cl'une malaclie du legionnaire nosocomiale onl ete obsenres. Le taux de mortalite a ete de 64 % . La moitie des patients ont developpe une maladie du legionna ire nosocomiale dans les trois semaines suivant leur aclrrtission. II a ete sw·prenant de cons tater Ia faiblesse des ta ux de corroboration des resultats a J'examen physique. en depit du fait que 52 % des patients presentaient des signes a Ia radiographic pulmonaire. Plus de Ia moilie des patients presentaient une maladie pulmonaire pre·eldstante qui rendait impossible le diagnostic radiograph ique de pneumonie atlribuable a Legionellapneumophila dans 16 % des cas. malgre une confirmation mlcrobiologique. Dix·neuf pour cent des patients chez qui ont ava il fait des hemocultures presentaient un autre organism e pathogene que L pnewnophila. suggerant une double infection chez certa ins d'entre ewe Lorsque les resultats cliniques et radiographiques ont ete combines. on a pu noter que 40% des patients presentaient run des trois mocleles associes a Ia maladie clu legionnaire nosocomiale. une opacite lobulaire de pneumonic a progression rapicle et de multiples opacites periphei;ques . Cependanl. chez 60 % des patients. aucune caracteristique distinctive n·a ete notee.

Departments of Medicine and Microbiology. Dalhousie Un iversity: and the Victoria General Hospital. Halifax. Nova Scotia Correspondence and reprints: Dr T J Marrie. Room 4090 ACC. Victoria General E-iospi.tal. 12 78 Tower Road. Halifax. Nova Scotia

B3H 2Y9 Received for publication May 6. 1991. Accepted August 9 . 1991

CAN J INFECT DIS VOL 3 No 5 SEPTEMBER/OCTOBER 1992 253

MARRIE eta/

SHORTLY AFTER ITS ISOLATION IN 1977 ( I ) IT BECAM E EVI

de nt. tha t. Legionella pneumophila caused nosocomial pneumonia (2 -7). Its ada ption to an aqua tic ecological environment has led. in part., lo its s u ccess as a n osocomia l pa thogen (8- 10). Contamin a ted pola ble water has been s hown to be a so urce of legionella in ma ny hospitals (ll -14). a nd erad ica tion of the microorganis m from the wa ter s upply has resulted in cessation of outbreaks (14). Despite ma ny descrip tions of the epidem iology of nosocomia l legionellosis ( 11 - 14). there h ave been very few s tud ies that. have llied lo cha racterize d istinctive cl inical presen ta tion s of th is form of nosocomial pneumonia.

Th e a u thors h ave identified cases of nosocomia l Legionnaires· d isea se at their ins ti tution since 198 1. In the presen t paper they describe their experience wiU1 55 cases oftilis illne sand emphasize recognition of its different. clinical presentation s .

MATERIAlS AND METHODS Case det e ctio n : From 1983 lo 1987 (1 5) U1e present a u thors performed serological testing for L pneumophila on all patients wi th nosocom ia l pneumonia. In a dd ition . fro m 1981 to 199 1. pa ti ents wiU1 nosocomia l pneu monia have been investigated for L p neumophila a t. Lh e d isc retion of their attending physician s a n d infec tiou s d isease cons u ltants. Knowledge of the presence of legion ella in the hospitar s pota b le water is widespread a nd p rompts efforts to identify cases of nosocomia l Legionnaires· disea e . Using the defin ition s given below. 55 cases of n osocomial Legionnaires· d isease were diagnosed. For ty of these were s tudied prospec tively . Da ta on the remainder were collected throu gh a retrospective cha r t. review. For each pa ti ent. the symptoms p resen t. a l onset. of pneumonia we re recorded . Case definit ion: Legionna ires· d isease was diagnosed if one or m ore of th e fo llowing c r ite r ia we re fu lfi ll ed : L pneumophila isola ted from respiratory secre tions . pulmonary tissue or p leura l fl u id: acute a nd conva lescen t. serum sam ples wiUl at least a fourfold rise in a ntibody

100

90

80

70

60 Percent

50

40

30

20

10

100

7<3

653 ...... cumulative

563

$7 14 21 28 35 42 49 56 63 70 ~7 1

Nu mber of days following admiss ion that LD occurred

Figure 1) Nwnber of d ays af ter admiss ion to hospital that nosocom ia l Legionnaires · d isease (LD) was cliagnosecl. The percentage at variotLS time imerva ls as w ell as the cumulative percentage is shown

254

TABLE 1 Symptoms and signs in 55 patients with nosocomial legionnaires' disease

Symptoms

Fever

Cough

Dyspnea

Chills

Nausea

Vom itting

Diarrhea

Pleuritic c hest pain Signs

Mean temperature (°C±SD)

Mean respiratory rate (per m in±SD)

Mean pulse rate (beats/ min±SD)

Roles

Rhonc hi

Bronc hial breathing

TABLE 2

Number(%)

41 (75) 37 (67)

35 (64) 17 (31) 12 (22) 12 (22) 12 (22)

8 (15)

38. 74± 1.28 24.22±11.6 1 08 .4±20.87

44 (80)

13 (24) 9 (16)

Potential risk factors in 55 patients with nosocomial legionnaires' disease

Feature

Corticosteroid therapy

Antibiotic therapy p rior to onset of pneumo nia

Assisted ventilation

Surgery within two weeks of p neumonia onset

Malignanc y

Tobacco smoker

No immunosuppressive therapy

Aspiration observed

Number(%)

38 (69)

34 (62)

33 (60) 29 (53)

16 (29) 16 (29)

15 (27) 11 (20)

ti tre to a t. least. 1:128 (a h igh stable litre or a s ingle high litre we re not accepted as eviden ce of Legionnaires· disease): or a positive dir ect. fl uorescent a ntibody test for L pneumophila in respira tory secre tions or post mortem lung tissue . Isolation of L pneumophila: Ma teria l (s putum. endotrach eal secre tions . pleural fluid or lung tissu e) for cu lture was inocula ted onto 5% s h eep blood agar: buffered ch arcoal yeast extract agar (BCYE) con taining 0 . 1% a lpha -keto -glu ta rate and t:\¥0 selective media (one BCYE contain ing cefama ndole . polymixin B and a nisomycin a nd th e oth er BCYE containing polym ixin B. a n isomycin a nd vancomycin [Gibco Labora tories , Wis cons inJ) . All plates were incubated aerobica lly a t. 37°C

in a humidified atmosphere con taining 5% carbon dioxide for seven days and examined da ily . Colonies U1a t m orphologically resembled legionella were cultured onto blood a nd BCYE agar. Those tha t. fa iled lo grow on blood agar were examin ed by a d irect. fluorescen t a n ti body technique (16) u s ing L pneumophlla serogroup l

C AN J INFECT DIS V OL 3 No 5 SEPTEMBER/ O CTOBER 1992

antisera (Centers for Disease Control in AUanla . Georgia). Direct fluorescence antibody studies for L pneumaphila: Endotracheal secretions. lung tissue and pleural fluid were examined for L pneumophiLa serogroups 1 to 6 us ing the direct Ouorescent antibody technique desc1ibed by Cherry et al (16). Antibody titres to L pneumophila: Antibody ti tres to L pneumophila serogroup 1 were performed on acute and convalescent serum samples usincr an indirect fluorescent antibody lechniqu (17). Positive and negative controls were included with each run. All reagents for this test were obtained from U1e Centers for Disease Control in Atlanta. Georgia Review of ch est radiographs: All 55 patients had pneumonia diagnosed radiographically by a radiologist. Fifty had chest radiographs available at the end of the study: these were reviewed by one of the authors during July and Augustl990 ln order to correlate radiographic patterns with clinical presentation. Rapidly progressive pneumonia was defined as an increase in the size of the opacity at lea l 50o/o in 48 h . Chronic obstructive pulmonary disea e. pulmonary edema. pulmonary hemorrhage and interstitial fibrosis were diacrnosed on the basis of a combination of clinical and radiological criteria. Chronic obstructive pulmonary disea e is strictly a clinical rather than a radiological diagnosis. This term was used when the chest radiograph demonstrated flattening of the diaphragm and increased anteriorposterior diameter of tl1e chest.

RESULTS Fifty-five patients (33 males and 22 females; mean

age 58.6 years) had nosocomial Lecrionnaires· disease diagnosed from 1981 to June 1990. Thirty-five (64o/o) died. The diagnosis was made by: isolation of the microorganism (40): positive serology (12): direct Ouorescent antibody test (three). Thirty-eigh t of the iso late were L pneumophiLa serogroup l. one was serogroup 6 and one was Legionella micdadei.

Just over one-half of the patients (56.3o/o) acquired Legionnaire · disease within iliree weeks of hospitalization (Figure 1): however, two patients had been hospitalized for more than 71 days before they acquired Legionnaire · disease. The symptoms and signs that these patients exhibited are given in Table l. Selected demographic features are given ln Table 2. Of note is U1e large number of patien ts wh o were receiving corticosteroid therapy- 69o/o. An additional 16o/o received orne oU1er form ofln1munosuppressive therapy.1\ven

ty-nine per cent had a malignan cy and 60o/o required assisted ventilation. Observed aspiralion was surprisingly common. affecting 20o/o of patients.

Results of blood cultures are given in Table 3. 1\venty-eight per cent of those who had blood cultures done had a pailiogen isolated. Staphylococcus aureus was mo t common. followed by Escherichia coli. A vari-

CAN J INFECT DIS VOL 3 No 5 SEPTEMBER/OCTOBER 1992

Nosocomial Legionnaires' disease

TABlE 3 Results of blood cultures in 55 patients with nosocomial legionnaires' disease

Number who had blood cultures done

Negative culture

Staphylococcus aureus Escherichia coli Streptococcus pneumonia Streptococcus mitis Haemophilus influenzae

TABlE 4

Number(%)

47 (85) 34 (72) 4 (8.5)

2 (4.2) 1 (2.1) 1 (2.1) 1 (2.1)

Results of sputum cultures and special stains for pathogens other than legionellaceae in 55 patients with nosocomial l egionnaires' disease

Sputum cultures done

Staphylococcus aureus Candida albicans Pseudomonas aeruginosa No growth

Escherichia coli Proteus mirabilis Kleibsiella species

Citrobacter species

Enterobacter species

Acinetobacter species

Streptococcus pyogenes Streptococcus pneumoniae Enterococcus fecalis Pneumocystis carinii

TABlE 5

Number(%)

52 (95) 12 (23)

9(17.3) 6 (11.5) 6 (11.5) 5 (9.6) 5 (9.6) 4 (7 .7)

3 (5.8) 2 (3.8) 1 (1.9)

1 ( 1.9) 1 (1.9) 1 (1.9) 1 (1 .9)

APACHE score* and mortality in 51 patients with nosocomial l egionnaires' disease

Score Number who lived Number who died (% total)

Oto 9 2 1 (33)

10 to 14 6 5 (46)

15to 19 5 10 (66)

20to 29 5 16(76)

30to 34 0 1 (100) "Refer to reference 18

ely of microorganisms was isolated from respiratory secretions (Table 4). Eleven per cent of the sputum samples showed no growth. SLaph aureus was iso lated from 23o/o of palienls. Fifty per cent had an aerob ic Gram-necrauve microorganism isolated. The auU1ors were unable to distinguish colonization from infection. Table 5 correlates the APACIIE score ( 18) with mortality. While the numbers in each category are small. there is an increase in mortality with increasing score.

A comparison of patients who lived with those who died revealed U1at those who died were more likely to

255

MARRIE eta/

Figure 2) Lobar type pneumonia due to Lcgionella pneumophila. This patient alsoju!filled the criteria for rapidly progessive penumonia

Figure 3) Chest radiograph qf a patient with nosocomial Legionnaires· disease with multiple peripheral and rounded opacities

have legionella isolated (29 of 35 versus nine of 20

IP<O.O 11) and to have rapidly progressive or lobar pneu monia (17 of 35 versus tv.ro of 20 IP<O.O 11).

Twenty- ix of the 50 patients (52%) who had chest radiographs available for review at the end of U1e study showed consolidation . Patchy opacities were present in 15 (30%) and rounded opacities were seen in eight (16%). Diffuse alveolar disease was present in eight (16%) and a pleural effusion in five (10%). Cavitation was observed in two (4%). A major finding was U1 e presence of pre-existing lung disease in 29 patients (58%). Chronic obstructive pulmonary disease was most common (14 or 48%). followed by interstitial fibrosis. pulmonary edema and pulmonary hemon-hage (U1ree each). Other finding included pleural effusion

256

TABLE 6 Comparison of selected features of nosocomial Legion-noires' disease from three reports

Present Feature Korvick et al* Kirb et alt study

Number studied 65 20 55 Male:female ratio 62:3 14:6 33:22 Mean age (years) 59.2 52.3 58.6 Number died 16 (24.6) 14 (70) 35 (63.3) Immunosuppressed 27 (41.5) 18 (90) 40 (73) Malignancy 19 (29) 7 (35) 16 (29) Assisted ventilation NS NS 33 (60)

Cough 60 (92) 14 (70) 37 (67) Chills 50 (77) 6 (30) 17 (31) Diarrhea 30 (47) 3 (15) 12 (22) Dyspnea 23 (36) 7 (35) 35 (64) Chest pain 21 (33) 11 (55) 8 (15) Hemoptysis 22 (34) 6 (30) 1 (2)

Legionnella isolated 5 (8) NS 40 (70) Numbers in brackets refer to percentage; 'Reference 20; 1 Reference 21 NS Not stated

and pre-existing pneumonia (two each) . and one each of bronchial stenosis and metastatic carcinoma.

When clinical and radiographic features were combined . the following patterns emerged: nonspecific pattern. 14 (30%): lobar pneumonia. ll (20%): rapidly progressive pneumonia, eight (16%): aspiration. three (6%): pulmona1y embolus, two (4%): and multiple peii pheral opacities. four (8%). The authors were unable to determine a specific pattern due to pre-existing lung disease in eight (16%). Examples of the various radio graphic patterns are given in Figures 2 to 6. Figures 7 and 8 illustrate the clinical course and radiographic features of one patient.

Twenty-eight patients had acute and at least four week convalescent serum samples collected. Twenty-one (75%) showed at least a fourfold rise in antibody li lre.

DISCUSSION There have been many reports of nosocomial Legion

naires· disease. Korvick and co-·workers (19) reviewed 16 reports of nosocomial legionellosis published from 1965 lo 1983. Only four of U1e reports described more U1an 40 patients. The mortality rate ranged from 17 to 66% . The major underlying diseases were immunocompromised stale. maJicrnancy and chronic lung dis ease . Legionella was isolated from U1e environment in 14 of the 16 reports and in 12 of these 14. isolation was from potable water. Korvick and Yu (20) in another report noted that surgical patients represent 23 to 50%

of all patients with nosocomial Legionnaires· disease. Fifty-three per cent of the present patients had undergone surgery within the two weeks prior to the onset of nosocomial pneumonia.

Table 6 summarizes selected data from two other studies of nosocomiallegionellosis (21.22) so that ready

CAN J INFECT DIS VOL 3 No 5 SEPTEMBER/OCTOBER 1992

Nosocomia l Legionnaires' disease

29/08/85 Figure 4 ) Chest radiog raphs showing consolidation of the entire right lung due to Legionella pneu mophila

Figure 5) Serial chest radiographs of a patient w ith Pneumocyslis ca1·inii pneumonia. On April 21. 1989. the patient clinically dete1iorated and Legion ella pneumophila was isolated. This ser ies illustrates the effect of underly ing lung d isease on the interpretation of change due to irifection with L pneumophila

CAN J INFECT DIS VOL 3 No 5 SEPTEMBER/OCTOBER 1992 257

MARRIE eta/

13-03-89

15-03-89

Figure 6) Serial chest radiographs of a 69-year-old male admitted Pebmary 21. 1989 with an exacerbation of chronic lung disease. The chronology of his course in hospital is shown in Figure 7

comparison can be made with the present. patients. The study by Kirby el al (21) involved an outbreak in a Veterans· Hospital in Los Angeles. California; the oU1er two sludie involved patients wiU1 sporadic nosocomial Legionnaires· disease. There are differences in mortality rates and in the percentage of patients who were immunosuppressed in Ule three studies. A major difference in the clinical manifestations i U1e low rate of hemoptysis in the present study. compared with about. one-lliird or patients in Kirby's study (21) .

Of note is the low number of patients in Lhe present. study wiU1 bronchial breathing (nine 116%]). However. 26 (52%) had an air bronchogram visualized radiographically. This is the clas ical radiographic sign of pneumonic consolidation (23).

Nine of the present. patients had positive blood cultures suggesting that. at. lea t 16% or patients had dual infections . Isolation of a vatiety of paU1ogens other U1an

258

legionella from the sputum in most instances probably refl t.s colonization of the respiratory tract of seriously ill patients. Pneumocystis carinii, however, was responsible for pneumonia in the patient who had U1e organism in U1e respiratory secretion. and it is likely that at lea t some of the other pathogens also caused the pneumonia. lt is equally possible that in some instan ces legionella may have been a colonizer and not a paU1ocren.

The APACHE ll score is a severity of disease classification U1at uses the initial values of 12 routine physiolocri cal measurements, age and previous health status to provide a general measure of severity of disease (18). Knaus and co-workers (18) validated this system for 5815 intensive care admissions from 13 hospitals. While the maximum score possible is 71. no patient has exceeded 55. A key finding in Knaus·s study (18) was the significant increase in death rate for each five-point

C AN J INFECT DIS V OL 3 No 5 SEPTEMBER/OCTOBER 1992

(_) 0

w a: ~ f<t a: w 0....

Nosocomial legionnaires ' d isease

~ w f-

40 39 38

37 36 ~~----~--~---r--~--~~--~~~

21 FEB

28 6 MAR

AMPICILLIN CLOXACILLIN

I. V. _____, P.O.

TOBRAMYCIN CEPHAMANDOLE ER YTH ROMYCIN

1-----1

500 160 64 SOLUMEDROL

RIFAMPIN CEFTAZIDIME

SPUTUM CULTURE

BLOOD CULTURE

(_) CD

s _J -"' 0 ..-X

p.o.

S. M aureus ar.

2 .P .aer. DFA-

cult-

7 8

P. aeru .

9 10 1 1 12

SOLUCORTEF

1--------l

_l RneumoRhila 1 +

C. albicans [branch]

13 14 15

_E.++ aeru. yeast +

+ DOPAMINE

P. aeru .

Creatinine normal until 14th 1:512

1/4 S. !iQ.i

1 :128

Pancytopenia and Leucoerythroblastic picture

Figure 7) In-hospital course of a 69-year-old male admiLLed February 21. 1989. with an exacerbation of chronic lung disease. An admission chest radiograph showed only chronic obstructive lung disease. The patient became febrile on March 7. 1989. and Legion e lla pneumophila was isolated from a sputum sample obtained on March 9. 1989. The infectious d isease consultant who saw the patient on March 9 made a clinical diagnosis of nosocomial Legionnaires· disease. At autopsy. there were severe emphysema. bilateral lobar pneumonia and bilateral microabscesses. Gram-positive cocci and yeast were seen on microscopic examination of the lungs. C Candida: N Intravenous: L Legionella: P aeru Pseudomonas aeruginosa: PO Per ora (by mouth): S Staphy lococcus: S epi Slaphylococcus epiclermidis: WBC White blood cell count

increase in score. In general. nonoperative patients had higher mortality rates at each score than d id postoperative patients. The present patients had higher mortali ty rates in each interval U1an did patients wiU1 various diagnoses in U1e report by Knaus et a l (18) . This observation holds true even when the s u bset of U1eir patients

C AN J INFECT DIS V OL 3 No 5 SEPTEMBER/OCTOBER 1992

with resp iratory fa il u re from lnfection is compared with the present cases of nosocomial Legionnaires' disease. Whi le U1e num ber of patients in the present study is small. it seems that a pneu monia-specific scoring system shou ld be developed.

The rad iographic mani festations of nosocomial

259

MARRIE eta/

Legionnai res· disease have been reported by a number of investigators (2 1,22). However, they did not report on pre-existing lung disease. Fifty-e igh t per cen t of the present patients had pre-existing disease. often lo s uch an extent that the a u thors were unable lo differen tiate the changes cl ue to legionella infection from the primary d isease process. Wh en the radiogra phic pictures were combined with the clinical data. three patterns emerged that were suggestive of nosocom ial Legionnaires· disease: lobar opacity. rapidly progress ive pneum onia a n d mu ltiple peripheral opacities. However. these three patterns accounted for only 40% of cases. Thus. there is nothing to distinguish most cases of nosocomial Legionnaires· disease fro m other types of nosocomia l pneumonia.

ACKNOWLEDGEMENTS: Th is research wa supported by grant MT 10577 from the Medical Re em·ch Council of Canada. We thank Ms Rhonda Grandy. RN. for data collection an d M s Lisa Tumer-Troltier for help wi th data processing. We are grateful lo the staff of lhe respiratory microbiology laboratory for isolation of legionella.

REFERENCES l. McDade JE. Shepard CC. Fraser DW. el al. Legionnaires·

disease. lsolalion of a bacterium an d demonstration of i ls role in oU1er respiratory d isease. N Eng! J Med 1977:297:1197-203.

2. Thacker SB. Ben nell JV. Tsai T. cl al. An outbreak in 1965 of severe respi ratory illness caused by Legionnaires· eli ease bacterium. J In feel Dis 1978:238:5 12-9 .

3. Brennen C. Vicker RM. Yu VL. Punlereri A. Yce CY. Discovery of occult legion ella pneumonia in a long slay hospital: Results of prospective serological stu dy. Br Med J 1987:295:306· 7.

4. Muder RR. Yu VL. McClure J. cl al. Nosocomia l Legionnaires· disease uncovered in a prospective pneumonia study: Implications fo r under diagnosis. JAMA 1982:249:3184·92.

5. Yu VL. Beam TR. Lumish RM. el al. Routine cu l lurin<f for lcgionella in the hospital environment may be a good idea: A three-hospital prospective study. Am J Mcd Sci 1987:30:97-9.

6. Marshal W. Fosler RS. Winn W . Legionnaires· disca c in renal transplant patients. Am J Surg Sci J 981: 141:423.

7. Saravolatz L. Pohlod D. Helzer. et al. Legionclla infection in renal transplant recip ients. In : T hornsbcny C. Balows A. Feeley JC. el al. eels. Legionclla : Proceedings of the 2nd International Symposium. Wa hinglon: Amel'ican Society for M icrobiology. 1984:23 J -3.

260

8. Fliermans CB, Chee1y WB. Onison LH . Smi l h SJ. T ison DL. Pope DH . Ecological d isll'ibu tion of Legionella p neumophila . Appl Environ Microbial 1981:4 1:9- 16.

9. J oly J R. Brissinot M. Duchaine J , el al. Ecological distribution o f legionellaceae in the Quebec ci ly area . Can J Microbial 1984:30:63-7.

10. Tobin JOH. Swann RA, BarUel l CLR. Isola tion of Legionella pneumophila from water system s: MeU1ods and prelim inaty results . Br Mecl J 198 1:282 :5 15-7.

ll. Guiguel M , Pierre J . Brun P. Berth elot G. Gollot A. Gibert C. Valleron A. Epidemiolo<fica l sunrey of a maj or outbreak of no ocomial legion ellosis. lnl J Epiclemiol 1987:16:466-71.

12. Palmer SR. Zamil'i I. Ribeiro CD. Gajewska A. Legionnaires' disease cl u ster and reduction in hospital hot water temperatures. Br Med J 1986:292: 1494-5.

13. Besl M. Yu VL. Stout J . Goelz A. Muder RR. Taylor F. Legionellaceae in the hospi tal water supply. Epidemiological link wilh d isease and evalu ation of a m eU1od for control of nosocomial Legionnaires· d isease and Pittsbu rgh pneumonia. Lancet 1983:307- 10.

14. Helms CM. Massanari RM. Zeitler R. el al . Legionnaires· disease associated with a h ospilal water system : A clu ster of 24 nosocomial cases. Ann In tern Med 1983:99 :1 72-8.

15. Mani e TJ . MacDonald S, Clarke K, Haldan e D . Nosocomial Legionn aires· d isease- Lessons from a four-year prospective study. J Infect Con l 1991 :19:79-85.

16. Cheny WB. Pi l l man B. Han is PP. Hebert GA. Thom ason BM . Weaver RE. Detection of Legionnaires· disease bacteria by d irect immunonuorescenl staining. J Clin Micro b ioi 1981:14:298-303.

17. Wilk inson HW. Fikes BJ. Cw ce D. Ind i rect im munonuorescence lesl for ser odiagnosis of Legion naires· disease: Evidence for serogroup d iversity of Legionnaires· d isease bacletial antigen s and for mul tip le specificil)' of h uman antibod ies . J Clin Microbial 1979:9 :379-83.

18. Kn aus WA. Draper EA. Wagner DP. Zimm erman JE. APACHE II: A severi ty of d isease classification system. Cril Care Med 1985:13:818-29 .

19. Korvick JA. Yu VL. Fang G-D. Legionella species as h ospi tal -acquired respiralOty pathogens. Semin Respir lnfecl 1987: 11:34-47.

20. Konrick JA. Yu VL. Legionnaires· disease: An emerging su rgica l p roblem. Ann T h orac Surg 1987:43:34 1-7.

2 1. Kirby BD. Snyder KM . M eyer RD. Fin egold SM. Legionnaires· d isease: Repor t of siA1.y-five nosocomially acquired cases and review of the li teratu re. Medicine 1980:59:188-205 .

22. Helms CM . V iner JP. Weisenburger DD. Chiu LC. Renner ED. Johnson W. Sporad ic Legionnaires· d isease: Clin ica l obsenrations on 87 n osocomial and commu nity-acquired cases. Am J Med Sci 1984:288:2-12.

23. Infectious d iseases of the lungs. In: Fraser RG. Pare JA. Pare PD. Fraser RS. Genereux GP. eels. D iagnosis of Diseases of U1e Chest. 3rd edn. Toronto: WB Sau nders. 1989:83 1.

CAN J INFECT DIS VOL 3 NO 5 SEPTEMBER/OCTOBER 1992

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