A Prspective Study f Cmmunity-Acquired Pneumnia in Hng Kng* Christpher H. S. Chan, M.B., F.C.C.P.; Michael Chen, B.Sc.; and]seph lbng, M.D., F.C.C.P. A prspective study f cmmunity-acquired pneumnia in Hng Kng was carried ut between January and December, 988. Ninety adults (57 male) with a mean age f 57.3 years were admitted t the Prince f Wales Hspital with cmmunity-acquired pneumnia. The etilgicdiagnsisf pneumnia was made in 37 cases (4 percent). Pneumcccal infectin was diagnsed in patients (2 percent). The same number f patients had pulmnary tuberculsis presenting as acute pneumnia. It culd nt be differentiated frm ther causes f pneumnia n clinical and radilgic grunds, althugh pleural effusin and upper lbe invlvement were mre cmmn in patients with tuberculsis. Chlamydia species were identified in Rve patients (6 percent) and Mycpl&ma pneumniae was identified in three patients (3 percent). There was n case f Leginnaires' disease. The etilgic agent culd nt be identified in 59 percent f cases. The lw incidence f etilgic diagnsis f cmmunity-acquired pneumnia was prbably related t the widespread use f antibitics in private practice. Tuberculsis is an imprtant cause f cmmunity-acquired pneumnia in Hng Kng and this diagnsis shuld be cnsidered in patients wh fail t respnd t Rrst-Iineantibitics. (Cheat 992; 0:442-(6) mmunity-acquired pneumnia is a serius disease C and a cmmn cause f hspital admissin. Despite mdern therapy, there is cnsiderable mrbidity and a definite mrtality, ranging frm 6.7 t 8 percent in the United Kingdm and frm 6 t 24 percent in the United States..2 There have been several recent studies n adults admitted t the hspital abrad with cmmunityacquired pneumnia.':" These shwed cnsiderable gegraphic differences in the type and frequency f causative rganisms. T ur knwledge, there have been n similar studies in Hng Kng. A retrspective survey f pneumnia in the Prince f Wales Hspital during 987 shwed that the definite r likely etilgic rganism was identified in nly 2 percent fpatients, and many treatment decisins (including the chice f antibitics) were arbitrary" Since the lcal pattern f pneumnia may be very different frm thercuntries, accurate infrmatin n which ratinal treatment can be based is needed. We therefre carried ut a prspective study f cmmunity-acquired pneumnia in patients admitted t ur reginal hspital ver a perid fne year. lbtients METHODS Between January, 988 and December 3, 988, all cases f cmmunity-acquired pneumnia in adults requiring admissin t the Prince f Wales Hspital were <.'nsidered fr inclusin in the *Frm the Departments f Medicine (Drs. Chan and Pang) and Clinical Phannaclgy (Dr. Chen), Chinese University fhng Kng, Prince f Wales Hspital, Shatin, N.T., Hng Kng. Manuscript received February 4; revisin accepted June 20. Reprint requests: Dr. Chan, Department f Medicine, ltince f.wales Hspital, Shatin, NT, Hng Kng study. All patients had clinical features f acute lwer respiratry tract infectin and radilgic evidence fcnslidatin r shadwing suggestive f infectin. The fllwingwere criteria fr exclusin: () pneumnia distal t a brnchial bstructin due t a freign bdy r carcinma; (2) patients with cexisting disease in whm pneumnia was an expected terminal event. eg, patient bedridden as a result f previus strke ; and (3) immuncmprmised patients, including thse with hematlgic malignant neplasms, acquired immundeficiency syndrme (AIDS), r cexisting slid rgan malignant neplasms. Ninety patients were eligible. f whm 57 (63 percent) were male. The mean age was 57.3 years (range, 9 t 90 years). Frty-three patients (48 percent) were current smkers and fur patients (4 percent) were exsmkers. Labratry Investigatins Bld, sputum, and urine specimens were cllected frm the patients as sn as pssible after hspital admissin. Bld was taken fr culture and serlgic analysis. Sputum was cllected. with the help f physitherapy ifnecessary. The fllwing investigatins were perfrmed: () bacterial culture and antibitic sensitivity testing ; (2) pneumcccal antigen ; and (3) Ziehl-Neelsen staining. Urine was cllected fr micrscpy, culture, and detectin f pneumcccal antigen. Thrat swabs fr viral culture were taken at the time f hspital admissin and n day 3. Serlgic tests were repeated at tw and six weeks after admissin. Bld was cultured fr up t seven days (by the BACfEC 460 system), using 6B and 60 media. Other bacterial cultures were by standard methds. Pneumcccal antigen was detected by means f the S pneumnle latex agglutinatin test (Wellcgen. Wellcme Diagnstics). The fllwing antigens were used fr the detectin f serum antibdies by the cmplement fixatin test : adenvirus, influenza A and B, respiratry syncytial virus, parain8uenza, 2, and 3, Chlamydia species, Q fever, and Mycplasma pneumnle. Antibdies t LegineUa pneumphila sertypes and 7 were tested by the flurescent methd. Thrat swabs fr viral culture were cllected in Hanks' balanced salt slutin supplemented with fetal bvine albumin, penicillin, streptmycin, and gentamicin. Viral cultures were made in the fllwingcell lines: human fibrblasts, LLC MK2, MOCK, and HEP2. 442 Cmmunity-acquired Pneumnia In Hng Kng (Chan, Chen, Pang)
Table l-agenl8ldentified in lbtienta with Pneumnia Definite! Organism Number Prbable Percentage Bacterial Strvptcccus pneumniae 4rl 2.2 Mycbacterium tuberculsis 0 2.2 Hemphilu«influenzae 4 04 4.4 Staphylcccus aureus 4 04 4.4 ~ h e m Streptcccus l y t i c 2 02 2.2 Enterbacter 2 02 2.2 Pseudmnas aerugllo8ll 0. Acinetbacter 0. Ttal 3 52 34 " Nnbacterial" Chlamydia species 5 50 5.6 Mycplasma pneumniae 3 30 3.3 Ttal 8 Ml 8.9 Viral Influenza A 0. Influenza B 2 ~ 2.2 Parainfluenza 2 ~ 2.2 Ttal 5 50 5.5 N identifiable pathgen 53 59 Etilgic Diagnsis finfectin Criteria fr identifying the causative rganism were adapted frm thse used in the British Thracic Sciety study.i Pneumcccal infectin was cnsidered "definite" if the rganism was islated frm bld r pleural fluid r ifpneumcccal antigen was detected in urine, and "prbable" ifthe rganism was islated frm sputum r ifpneumcccal antigen was detected in sputum. Infectin with ther bacteria was cnsidered definite if the rganism was islated frm bld r pleural fluid, and cnsidered prbable when the rganisms were islated frm sputum. A furfld r greater rise in titer in any f the serlgic tests was cnsidered definite evidence f infectin. RESULTS Frty-five definite r prbable infective agents were detected in 37 patients (4 percent) (Table). The bacterial pathgen mst cmmnly identified was Streptcccus pneumniae ( patients). The diagnsis f pneumcccal infectin was definite in fur patients: ne had a psitive bld culture (the nly psitive bld culture in the whle study), and pneumcccal antigen was detected in the urine f three thers. The diagnsis f pneumcccal infectin was prbable in seven patients : the pathgen was detected in their sputum specimens by culture and/r by the presence f pneumcccal antigen. A diagnsis f pulmnary tuberculsis was made in patients. Acid-fast bacilli were seen in Ziehl Neelsen stains f sputum frm eight patients. One patient was smear negative but culture psitive fr Mycbacterium tuberculsis. Tw cases were subsequently diagnsed after brnchscpy and pleural bipsy, respectively. Three f the patients had a histry f previusly treated pulmnary tuberculsis. Hemphilus influenzae was cultured frm sputum in fur patients, Staphylcccus aureus in fur, J3- HemphUus influenwe Staphylcccus aureus Mycbacterium tuberculsis KlebsieUa pneumniae Table 2-Mi%ed Infectins HemphUus influenwe Influenza B Parainfluenza Staphylcccus aureus Influenza A Chlamydia species Chlamydia species Acinetber ~ h e m streptccci l y t i c Enterbacter Candida alblcans hemlytic Streptcccus in tw, Enterbacter in tw, Pseudmnas aeruginsa in ne, and Acinetbacter in ne. Nne f these rganisms culd be islated frm bld r pleural fluid. Chlamydia species were the mst cmmn rganisms identified by paired sera (five patients), fllwed by M pneumniae (three patients), influenza B (tw patients), parainfluenza (tw patients), and influenza A (ne patient). N case f L pneumphila was identified. Multiple rganisms were implicated in 2 patients (Table2), but the etilgic significance f sme f the rganisms is unclear. Fr example, it is dubtful whether the presence f Candida albicans in a patient whse sputum als grew Klebsiella pneumniae, and the culture f varius rganisms in a patient with tuberculsis wuld suggest a pathlgic rle fr thse rganisms that wuld therwise be cnsidered "cmmensals." A histry f antibitic administratin was btained in 7 patients (9 percent) befre hspital admissin. The remainder (8 percent) either did nt knw r were unsure whether they had received antibitics. Twenty-seven patients (30 percent) had a histry f preexisting chest disrders (Table 3). One patient had a histry f lung carcinma treated by lbectmy fur years befre and ne had small-cell lung carcinma treated by chemtherapy tw years previusly. Bth f these had n evidence f recurrence n this hspital admissin and bth respnded favrably t antibitic treatment. A cexisting systemic disease was fund in 6 patients (9 percent) (Table4). Table 3-Pnle%isting Cheat Diarders N. % Chrnic brnchitis 2 3 Old tuberculsis 0 Brnchiectasis 2 2 Carcinma (treated) 2 2 Asthma Ttal 27 30 N. I CHEST I 0 I 2 I FEBRUARY, 992 443
Table 4-Auciated Syatemic Diardera Cardivascular disease Diabetes mellitus Central nervus system disease Cnnective tissue disease Previus nnpulmnary neplasm Others Ttal Fur patients (three female, ne male) died, giving an verall mrtality rate f 4 percent. Three patients were ld, aged 73, 75, and 89 years, respectively. One f them was a lng-term smker fr 60 years and anther had insulin-dependent diabetes mellitus. Nne was a lng-term alchlic. The yungest patient wh died was a 3-year-ld wman with plimyelitis in childhd. She went int respiratry failure due t extensive pneumnia invlving bth lungs but n pathgen culd be identified. She died despite cmbinatin antibitic therapy and assisted ventilatin. A mixed grwth f P aeruginsa, K pneumniae, and C albicans was islated frm the sputum f ne patient. N pathgenic rganism can be identified in the ther three. A cmparisn f the characteristics f tuberculus and nntuberculus pneumnia was made (Table 5). The mean age f the tuberculus patients was lwer than the nntuberculus patients. The incidence f diabetes mellitus and histry f tuberculsis was mre cmmn in patients with tuberculsis but the difference was nt statistically significant. Hwever, the presence f pleural effusin (p<o.05) and upper lbe invlvement n chest rentgengrams were mre frequent in patients with tuberculsis (p<o.ooi). DISCUSSION In this study, we wereablet identifythepathgenic rganism in 37 patients nly (4 percent). This is lwer than that reprted in ther cuntries with results ranging frm 49 percent t 97 percent.y The percentage f pneumcccal pneumnia in ur grup f Table 5-A CmpariaOR afthe Characteriaticaf Tuberculua and Nntuberculua Pneumnia Sex Age, mean, yr N. f patients with Diabetes mellitus Histry f tuberculsis Chest rentgengram with Pleural effusin Upper lbe(s) invlvement *p<o.ol. tp<o.05..tp<o.ooi (X. test with Yates' crrectin). 8 8 2 9 Tuberculus Nntuberculus n= n=79 7M,4F 42.2* (9.%) 3 (27.3%) 3 (27.3%)t 9 (8.8%)t N. 7 7 2 7 5OM,29F 59.4 6 (7.6%) 7 (8.9%) 4 (5.%) (20.3%) patients was 2.2 percent. This was much lwer than studies frm ther cuntries that revealed S pneumniae as the pathgen in 5 t 76 percent f cases..2.4-7 'The nly exceptin was a reprt frm the United Kingdm that shwed that S pneumniae was the cause f pneumnia in.5 percent f cases," It is ntewrthy that 57 percent f patients in that study had received antibitics befre hspital admissin. This figure was much higher than ther reprts. Sputum specimens were btained frm 84 patients (93 percent). Sme f these were unsatisfactry and might accunt fr the lwer detectin rate in ur series. Hwever, a mre likely reasn was treatment with antibitics befre hspital admissin. Previus studies had shwn that the chance f btaining a psitive sputum culture IS much lwer after antibitic treatment." It is a cmmn prblem in Hng Kng that patients tend t cnsult mre than ne physician within a very shrt perid, and dcumentatin tends t be inadequate utside the hspital.0 The patients are frequently nt tld what drugs are prescribed and drug cntainers are mstly unlabeled. Therefre, althugh nly 7 patients (9 percent) gave a histry f antibitic treatment befre admissin, it is very likely that a large prprtin f the remaining patients had als received antibitics. Earlier reprts suggested that pneumcccal antigen detected by latex agglutinatin is a sensitive and specific test fr diagnsis f pneumcccal pneumnia. II Hwever, a psitive sputum culture f S pneumniae was btained in nly tw f five patients with psitive sputum pneumcccal antigen and in nne f three patients with psitive urinary pneumcccal antigen. In ttal, six patients had psitive sputum r urinary pneumcccal antigen, but S pneumniae culd nt be islated frm sputum r bld. Therefre, mre than half f the cases f pneumcccal pneumnia culd be diagnsed nly by pneumcccal antigen test. It had been shwn that this test gave fewer psitive results in patients wh had received antibitics. I Therefre, it is pssible that the actual number f cases f pneumcccal pneumnia in ur grup f patients might be higher than we bserved. This interpretatin is further supprted by the study f Farr et al l2 that in patients in whm the micrbial cause was nt determined, the mst likely rganism was S pneumniae. Furthermre, in ur retrspective study f cmmunity-acquired pneumnia," mst patients respnded rapidly t penicillin r ampicillin nly. This wuld be expected if the predminant causative rganism was the pneumcccus. Nevertheless, the lw psitive identificatin rate was disappinting, and finn cnclusins culd nt be drawn regarding the true rate f pneumcccal infectin. The mrtality rate f 4 percent in the present study was similar t the earlier retrspective study in Hng 444 Cmmunlty-acquired Pneumnia in Hng Kng (ChlIn. Chen, Peng)
Kng that revealed a mrtality rate f 2 percent. This was lwer than that reprted in ther cuntries that varied between 5.7 and 24 percent.'> One f the reasns fr the lwer mrtality rate in-ur study -is that we had excluded patients with immunsuppressin, which may accunt fr a significant number f deaths in ther studies." Likewise, patients with pstbstructin pneumnia, cexisting malignant neplasms, and patients in whm pneumnia is a likely terminal event were excluded frm ur study. In additin t ur strict selectin criteria, antibitic treatment prir t hspital admissin might play a part als. A previus study in the United Kingdm I had shwn that in patients with pneumcccal pneumnia, the mrtality rate was lwer in thse wh had received antibitics befre admissin. N difference had been fund fr ther rganisms. If S pneumniae was.an imprtant pathgen in cmmunity-acquired pneumnia in Hng Kng as we suspect, previus treatment with antibitics wuld reduce nt nly the chance f btaining a psitive diagnsis, but may als reduce the mrtality rate. Althugh S pneumniae is the mst cmmn cause f cmmunity-acquired pneumnia in many cuntries, there are cnsiderable gegraphic differences in the incidence f ther pathgens." Mycbacterium tuberculsis was the secnd mst cmmn pathgen identified in ur grup f patients (2 percent). A similar high incidence f tuberculsis (0 percent) amng subjects presenting with acute pneumnia had been reprted in France. 6 Since nly patients wh presented with features f acute pneumnia were included and thse with a chrnic illness r typical radilgic changes suggestive f tuberculsis were excluded, a significant number f cases f pulmnary tuberculsis culd nt be differentiated frm ther causes f acute pneumnia n clinical r radilgic grunds. The presence f pleural effusin and upper lbe invlvement favrs tuberculsis, but these features are by n means specific. Therefre, pulmnary tuberculsis shuld always be seriusly cnsidered in the differential diagnsis f acute pneumnia in Hng Kng, and we suggest that sputum shuld be examined rutinely fr tubercle bacilli in this grup f patients. If there is any dubt, especially if the patient fails t respnd t initial antibitic treatment, mre invasive prcedures such as brnchscpy r pleural bipsy (if there is a effusin) shuld be perfrmed early t btain a definitive diagnsis. Failure t make a diagnsis f tuberculsis may be disastrus and it is nt uncmmn that the diagnsis f tuberculsis is made nly at pstmrtem examinatin.p-" Chlamydia species were the mst cmmn nnbacterial cause f cmmunity-acquired pneumnia. The incidence f 5.6 percent in ur study was higher than that reprted elsewhere, the nly exceptin being a reprt frm Nttingham, United Kingdm." In that study, Chlamydia psittaci was identified as the pathgenic rganism in 5.5 percent f cases f cmmunityacquired pneumnia. It has been estimated that apprximately halfthe cases f psittacsis are reprted in wners f pet birds, whereas a quarter f the patients can prvide n histry f expsure t birds. 5 In cntrast, nne f the five patients in ur series gave a histry f cntact with birds r pultry. This raises the pssibility that sme r even all f them might have pneumniadue t C pneumniae (strain TWARI6), which is a primary human pathgen withut a bird r animal reservir. It is distinguished frm C psittaci n ultrastructure and DNA analysis but cannt be differentiated by the cmplement fixatin test that we used in this study. The incidence f pneumnia due t Chlamydia species in ur study is 5.6 percent and this cncurs with the impressin that the TWAR agent is a cause f 6 t 2 percent f cmmunity-acquired pneumnia wrldwide. 7 Mycplasma pneumnia was uncmmn in ur series. Epidemics f Mycplasma pneumnia ccur every three t five years in the United Kingdm;'? but n knwn epidemic had been reprted in Hng Kng. Likewise, Leginnaires' disease had nt been identified in ur patients. There were very few knwn cases reprted in Hng Kng, althugh the rganism is nt uncmmnly fund; fr instance, L pneumphila had been identified in sme f the water twers f the Prince f Wales Hspital. In summary, despite the use f currently available micrbilgic techniques, the etilgic agent was identified in a relatively small prprtin f patients with cmmunity-acquired pneumnia in Hng Kng. Previus administratin f antibitics in a large number f patients was prbably the reasn fr this. Nevertheless, there are sme features that suggest that S pneumniae may be the predminant rganism, as in ther studies. Mycbacterium tuberculsis and Chlamydia species, hwever, are imprtant rganisms identified in this study. 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