Crossreactivity of Candida With Pneumocystis

To th e Editor: VVe appreciate very mu ch th e com ments about our article conce rn ing the pro gnosis of Pneumocystis carinii pneumonia (PCP) in pat ients with AIDS, requiring mechan ical ventilation (MV) for ac ute respira tor y failure (ARF). Mech ani cal vent ilation for ARF secondary to PCP may be necessar v at different tim es relati ve to ini tiation of effective cotrimoxaz~le-methylpredn isolone com bina tion th era py. Ind eed , it is essential to distin gui sh the pati ents in th erapeuti c failure, ie, wh ose ARF worsens despite an a pprop riate treatment of at least 5 days.' In our opinion, th e progn osis of these patients is d ram atically poor and MV m ay not be justified . Th ese pati ents must be clea rly differ entiated from those with inaug ural ARF or ARF that begi ns in the first days of a treatm ent whi ch has not yet reached efficacy. Such pati ents full y justify recour se to MV. Our result s clearl y show th ese data with a survi val rate of 50 percent among ventil at ed pati ents who received less than 5 days of cot rim oxazole-me thylpred nisolone combination therapy, and with a survival rate of 4 percent among ventil at ed pati ents intubated aft er 5 days of treatm ent. No oth er pro gn ostic factors (age, sex, symptom duration prior to treatment , Pa02 on ad m ission, lactate dehydr ogenase level on admission, simplified ac ute ph ysiology score, PE EP , .. .) wer e found . Our results differ from som e recent stud ies, although severa l authors still rep ort sur vival rates of less th an 10 per cent. 2,3 Thi s discrepancy may be relat ed to th e absence of this kind of stratification acco rd ing to th e delay betw een the beginning of th e med ical treatm ent and the institution of MV. It wouid be interesting if thi s stra tification could be used by other gro ups, in particular with North Ame rica n patients. Fredert k Stai kouis ku, M .D ., Bertrand Cu idet , MD ., Charles M. Mauaud, M.D ., and Georges Offens tad t, M .D ., Paris, Fran ce R EFERENCES

Masur H. Prevention and treatment of Pneum ocystis pn eum aniae. N Eng J Med 1992; 327:1853-60 2 Miller RF , Mitchell DM . Mana gem ent of respiratory failure in patients with the acquired immunodeficiency syndrome and Pneumocqsti s cari n i i pneumoniae. Thorax 1990; 45:140-46 3 McGladrey J, Ronco JJ, Russell JA, Lawson LM, McNeil N, Schecht er MT , et al. Changing out come of m echanically ventilated acut e respiratory failur e secondary to AIDS-related PCP . VI Int ernational Conference on AIDS. San Francisco, 1990, Th.B .405

Diagnosis of Pneumocystis carinii Infection in HIV-Seropositive Patients by Identification of P carinii in Pleural Fluid To th e Editor: We read with interest th e rep ort that appeared in th e Jun e 1993 issue of Ches t by Schaumber g et al' about the diagnosis of Pneumocqstis carinii by ide ntification in pleura l fluid in HIV infecte d pat ient s on aerosolized pent amidine pr oph ylaxis. We think that involvem ent of th e pleura is a main patt ern of breakthr ough P carin ii pn eum onia that has lar gely been unr ecogni zed. We observed an HIV-infect ed hem ophili ac pati ent pr esenting with a doubl e-sided pn eum othorax; on thora cotom y, th ere ap peared a th icken ed visceral pleura, three bron ch opleural fistula e, and a cyst. Pleural biop sy revealed P cari nii pleurltis.f Anoth er

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case of pleural involvem ent was rep ort ed by Dyner et al.3 Our path ogen etic conside ratio n is the conve rsion of a diffu se into a peripher all y localiz ed smo lde ring infection because of an nonhomogen eous deliver y of th e topic all y ad m inistered drug. Pneum oth orax in AIDS is difficult to mana ge. In our hem oph iliac cohort with 97 patien ts on ae rosolized pent amidine since Jun e 1989, five pneum oth ora ces cou ld be obse rved . Tw o were coincide nta l with a brea kthrough P carinii pn eumonia, anothe r occ ur red without any appare nt oppor tunistic infecti on during secon da ry prophylaxis. Another case was th e result of cavitating Pseud om ona s aeru ginosa pn eum oni a; anothe r pn eumothorax during primar y prophylaxis could not be att ributed to any und erl ying pulm onary di sease and was classified as sponta neo us. Although th e pleura is a tar get of P carin ii infection in th e settin g of aerosolized pentamidine proph ylaxis, oth er und erl ying conditions mu st be tak en into account. Yet recurren ces of P carinii pneumonia appear treatable. We, th eref ore, now recom mend an aggressive diagnostic and th er ap euti c approach in HIVinf ect ed patients with pneumoth orax during aero solized pentamid ine pr ophylaxis. This includes thoracoscopy with inspection of th e pleural surfaces, pleural biops y in case of an altered aspect, and eventually resection of cysts. As Sch aumberg et al! pointed out, examination of pleural fluid including a sta in for P earinii may add furth er useful diagnosti c inf ormation.

Santiago Eung , M .D., and [ iirgen Rockstroh , M .D., Universit y 0/ Bonn , Germ any R EFERENCES

Schau m berg TH, Schnap p LM, Taylor KG, Golde n JA. Diagnosis of Pneumocystis carinii infection in HI V-seropositive pat ients by identification of P carinii in pleural fluid. Chest 1993; 103:1890-91 2 Ewig S, v Kempis J, Rockstroh JK, Steudel A, Vogel J, Niese D. Pneumocystis carin ii pleur opneum onia after aerosolized pentamidine pr oph ylaxis. Infection 1991; 19:442-44 3 Dyner T, Lan g W , Busch D, Gordo n R. Intravascular and pleural involvem ent by Pneumocystis carinii in a patient with th e acquired immunodeficiency syndro me (AIDS). Ann Intern Med 1989; 111:94

Crossreactivity of Candida With Pneumocystis To th e Edit or: Dir ect im m unofluorescence monoclonal antibody (OFA) is one of the pr eferred meth ods of det ectin g Pneumocysti s cari nii in lower respir atory tract secre tions.' Th e OFA test has high spec ificity and sensitivity for the det ection of P carinii.2 Lik e other stai n interpre tations, however, results dep end on user experience and th e conce ntra tion of orga nisms. According to the manufactur er of our test kit, Gen eti c System s (Seattle), the test is not believed to crossreac t with other orga nisms like yeasts. H owever , we recentl v observed crossreac tivity with Ca nd ida . Th is prompted us to test the kit aga inst 33 fr esh culture s of clinica l and stoc k yeast stra ins, including 21 Candida albicans, 5 Candida glabrata, 4 Candida trop icalis, 2 Candida parapsilosis, and 1 Histoplasma capsulatum. Th e H capsulatum was included becau se it was closer in size to P carin ii th an Candida. No fluorescence was detected in 16 stra ins, 9 had fluorescence limit ed to 1 to 10 per cent of all cells observed, whil e 8 strai ns (2 C parapsilo sis and 6 C albican s } exhibited fluorescen ce in 20 to 80 per cent of th e cells. Communications to the Editor

We also wan ted to det ermine if crossreactivity occurred in recentl y collec ted expec tora ted sputum specim ens. Tw elve sputa with yeasts observ ed by Gram 's sta in were tested by DFA . Ten specim ens had 0 to 1 perc ent cells that showed fluorescence. Of th e remaining two specime ns, fluorescenc e was seen in 33 perce nt and 50 per cent of th e yeasts, respectively. Th e spec ime n in which 50 perc en t of th e yeasts showed fluorescenc e also had P carinii in m oder at e to heavy conce ntra tion, which allow ed dir ect compa rison of organisms. Although th e yeasts wer e larg er , th ey might ha ve been confused with P carinii by th e unexperienced observe r. This false-posit ive result is most likely du e to a comm on antigen / epitope in fun gi and P carinii, which has been reported by Lundgren et al." On e way to guard against misinterpretation of the DFA test is to perform a Gr am 's stain on th e same specime n. If th e Gr am 's stain is positive for yeasts, the observ er should be alerted to th e possibility of yeasts th at show fluorescence. Th er efore, th e purpose of this letter is to alert clin icians that the presence of Candida in sputa could be a sourc e of false-positive P carinii DFA test results.

Thoma s G. Cannon, M .D., and D. J. Flournoy , Ph.D., Departmen t of Pathology , Universit y of Oklahoma Health Sciences Cent er, Oklahoma City , Oklahoma REFERENCES

Wolfson JS, Waldron MA, Sierra LS. Blinded com parison of a dir ect imm unofluorescent m onoclonal anti bod y staining method and a Giem sa staining method for identific at ion of Pneumocy stis carinii in induced sputum and bronchoalveol ar lavage specime ns of patients infect ed with hum an immunodeficiency virus. J Clin Microbiol 1990; 28:2136-38 2 Stratton N, Hr yniewicki J, Aarnaes SL, Tan G, De La Maza LM, Peterson EM . Comparison of mon oclonal antibody and calcofluor white stains for th e detection of Pneumo cystis carinii from respira tory specimens. J Clin Microbiol 1991; 29:645-47 3 Lundgren B, Kovacs JA, Nelson NN, Stock F, Martinez A, Gill VJ. Pneumocystis carinii and specific fungi have a common epitope identified by a monoclonal antibody . J Clin Microbiol 1992; 30:391-95

TNF and Pneumonia To the Editor: Th e article by Mar ik et al,! which app ear ed in th e August 1993 issue of Chest, addresses an im portant and neglect ed area of resear ch. While there are many stud ies about septic shock, there ar e few ab out pneumonia. As th e authors explain, there is good reason to suspect tha t similar mechanisms are at work in both disorder s, and recently we hav e investigated the role of phagocyte function as well as cytokin e release in pneumonla.S" In our study,2 tumor necr osis fact or alpha (T N F-a ) was measured at inter vals of 24 hours during th e pati ent's admission. Onl y 41 per cent of our pati ent s had measurable T NF-a at an y point during their adm ission, and this oft en appea red or incr eased by the second or thi rd day in pati ents aft er th e start of antibiotic th er apy . Thi s discr ep ancy can probably be explain ed on methodologic grounds, since we used an enz ym e-link ed imrnunosorbent assay that mea sures fr ee T N F-a, ie, T NF-a which is not bound to circulating soluble receptors. It seems pr em ature to conclude th at antibiotics hav e no effect on T NF- a levels, and in our op inion , larg er studies ar e req uir ed to answer th is q uestion.

In relat ion to the pathogenesis of fatal pn eumonia, com pa rt men tali zation of TN F-a release would have bio logical advant age since it would isolate potenti ally damaging inflamma tory events in the lun g from ca using the system ic damage wh ich occurs in man y of those patients wh o die from com m unity-acq uired pn eumonia. Cou ld it be tha t the overspill of fr ee TN F-a pla ys a role in this proc ess? Whil e hydrocortis one tre atme nt does not a ppe ar to hav e had an effect in thi s study , other meth ods of int ervention ar e possible. Th er e is a need for more informa tion on th e pathogen esis of fatal com m unit y-acq uired pn eumonia, which remains a common ca use of death.

Ian A . Cree, M.B., Ch.B., Ph.D., M.R. G.Path., Department of Pathology , University of Dundee, Nine wells Hospital and Med ical School, Scotland; and John H. W int er, MD. , M.R.C.P. Department of Respiratory Medicine, King's Cross Hospital Dundee, Scotland R EFER El\'CES

Marik P, Kraus P, Sribante J, Havlik I, Lipman J, Johnson DW. Hydrocorti sone and tumor nec rosis factor in sever e com m unity-acquired pn eum onia: a randomized controlled study. Chest 1993; 104:389-92 2 Cree lA, Michie HJ, Moussa K, Winter JH , Stephens S. Sepsis and shock [letter]. Lanc et 1991; 338:1221-22 3 Moussa K, Michie HJ, Cree l A, MacCaff ert y A, Winter JH, Brown RA. Phagocyte fun ction and cyto kine production in commun ity-acquired pneumonia. Thorax 1994;49:107-11

To the Editor: We appreciat e th e comme nts made by Dr s. Cree and Wint er . Th e T NF- a levels in blood may not accurat ely reflect intra-alveolar levels in patien ts with pn eumonia as a result of the com partmentalized production of cytokines. We conside re d performing bronchoalveolar lavage , but thou gh t this to be un ethical in nonintubated hypoxic patient s. Furthermore, we measured total circulating T NF-a, rather than fre e biologic ally activ e TNF-a . These two factors may have affect ed th e result s of our study . Odio et al measured TNF-a in th e cerebrospina l fluid of patients with ba cter ial meningitis who wer e tr eated with cefotaxim e and either pla cebo or dexam ethasone'! Interestingly, th e T NF-a fell in both groups of pati ents; however , th e fall was m ore significant in th e de xam ethasone treated group (p = 0.04). We agr ee with Dr s. Cree and Winter, that there is a need for fur th er research on th e role of cytokines in the pathogenesis of fatal com m unity acquired pn eumonia.

Paul E. Marik, M .B.B.Ch., M .Med ., Wayne Stat e University, Michigan ; Peter A . Kraus, M.M.B.Ch., Regina , Canada ; and Ivan Havlik, Ph.D., Un iversit y of Witwatersand, South Afr ica R EFERENCE

Odio CM, Fainge zight I, Paris M, Nassar M, Baltodano A, Rogers J, et al. Th e beneficial effects of ea rly dexam eth asone ad m inistration in infants and children with bacterial m eningitis. N Engl J Med 1991; 324 :1525-31 CHEST I 106 I 2 I AUGUST, 1994

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