Pneumocystis carinii pneumonia in HIV-investigate or just treat ?

l'11c11111oc_n ti.1 ntri11ii p11eurn,mia (PC'P) is an cxln.:mdy ccin11rnm mani fcs ta1io11 of the ac4uircd irnrnu110<.k ticic 11cy syndrome (A ll >S) 1\:sulting f'ro111 i11fcct io11 wil h 1hc hunrnn i111munockfil·it:11cy virus (111 V ). Mm l episodes prcst:nl in a fa irly typical m;11111l'r wilh incrca,cd dyspnca ;1nd/nr a nnn1mitluc1i vc cough. a diffuse in1c rs1i1ial 1x1llern on chest 1 atliograph ;111<.l an ck, .t ll:d al veolar-arterial oxyge n gradi ..: 111. Tht: pallt:rn has hl'en so typical or the disorucr that c111pirical therapy wilhrnll rni..:rohiologit:al proof or disease i!-> nf'1c11 initialed hy pri1n;1r~ ,:arc physicians. This slra lcgy has 11ut hccn lt:sk'd i11 CP11tmllcd l'iinica l tria b although dccisio 11 ,1nalysi s 1nodl· h '1 :1vc at1 c111ptcd to cv,duatc it. It is like ly reasonahlc to choose empirit:al antirninohial therapy in specific clinica l scll ings , uch as: (a) typical ral.liographic pit:turc in a person with dyspnea and/or nonproductive cou!!h. pr..:sem:c or HIV and a ('1)4 counl of less than 200 ccl l~/mrn\ (hl previous PC P. typical appc ar;111ce and Lht: palie nl is known to to lerate standard an ti-PCP medications: and (c ) high clinica l !->U!->pici<in in a pat ient who refuses hronchoscopy yet dt:s ircs lrcallllt:rll or where broncho!->copy cannot he performed . However . ..::irly bronchoscopy shuulu strongly he considered when the d H.:s t rad iogr;1ph i!-. nut tyr,ical or{' rnri11ii inll:l'lion or rr there is failure 10 respond al'tcr a prnle tincd period.

In the earl y ye ars of management of H IV infected patients, microbiolog ical proof of infection with P rnrinii was so ught in vi rtually all patie nts.However.a strong argument can be made fo r empirical treatment based on clinical and radiographic suspicion of PC P. As well, there are invest ig ations that can be initiated to rai se or lower clinical suspicion g iven a hi story and chest racliograph compatible wi th PCP.T he li kelihood of PC P increases sign ifica ntly when the CD4 count falls below 200 cells/11111/ T he likelihood of PCP in the infected patient not receiv ing AZT ( Lidovudinc) or pneumocystis prophylax is gi ven a compatible history and x-ray is approximately 65 % if the CD4 rnunt is less then 200 cclls/nm1".However, with AZT and pnL•umocystis prophyla xis, that likdihood drops tu perhaps 40':

BRONCHOSCOPYVERSUS EMPIRICAL THERAPY
The most direct method for obtaining an adequate sample is fibreoptic bronchoscopy with bronclwal vL'olar la vage.T he sens itivity of bronchoscopy with bronchoa lvcol ar lavage exceed s 90% in vi rtuall y all studies.T he spcL' ilic ity is obviously e xcelle nt.T rans bro nc hial bi o psies add potential morbidi ty with little g a in in se ns iti vity .T he adva nt ages of ea rl y fibreopti c bronchoscopy include the ability to find other potential in fec tive agen ts tha t could be treatL'd , and not subj ecting a pati e nt to the potential and frequent side e ffcL'ts of ant imic robial the rapy for PC P. Furt he rmore .w he n the use or tri me th op rim-sulphamethox azo le is limited due to previous ad verse side effec ts. the a lternative agents (cg.pent a midine or the combination of clindamyc in and primaquine) do nut carry the broad antibacteri a l spec trum or trimcthoprim-s ulphamcthoxazole .An incorrectl y diagnosed episode of PCP may lead to m isdi ag nos ing so meone as having AIDS rather than si m pl y carry ing H IV. The d iagnosis of AI DS carri es a g reat psychological burdC'n as we ll as the potential addition of therapy with toxic and often un proven agents.Fina lly, it would be far simp ler, with less morbidity, tu conduct hron choscopy on a pati ent with mild disturbances in gas e xc hange rather tha n atte mpting bronc hoscopy in the patie nt who has deve lo ped severe respiratory distress follow ing failure uf anti -PCP age nts.T he advantage o f foregoing brnnchoscopy and initiating e mpirical the rapy incl ude a sio nificant cost saving, e liminating d iscomfort related to bronchoscopy and not subject ing medical personnel tu the risk of contamination with inrectcd body tluids.
A recent publication approac hed the quL'stion or bronchoscopy versus empi rical the rapy using the technique of ckcisiun ana lysis (6).The model was based \HI a patient not receiving pneu moc ys tis prophylaxi s presen ting with criteria sati sfactory for the CDC diagnosis of presumed PCP.Early bronchoscopy wi th treat me nt based on the brnnchoscopy results was compared with e mpirical treatment for PCP (trimethoprim-sulfametho xazolc o r pentam idine, and steroids) and clelayccl bronchoscopy in those not re sponding to fiv e clays o f tre atment.There was essenti a lly no d ifference in the ex pected one-month survival rates comparing both ma nageme nt strategics.T herefore.it was concluded tha t emp irical treatme nt would be a su perior strategy in thal specific sn:nario.gi ven that early bronchoscopy did not offer any addi tional survival bene fi t and was associated with additional costs and discomfort with possible morbidity to the patient.Unfo11unately, the study used bronchoscopy with hronchoalveolar lavage and tra nsbronchial biopsies.One could argue that transbronchial biopsies are not necessary, and there fo re not using them would decrease morbidity.As well, the study did not use a model in which patients received pncurnocystis prophyl axis, which would lower the estimated prior probability of PCP.lt could be argued that with aggressive use of trimethoprim-sulphamcthoxazole prophylaxis and the knowledge that it is a better prophylactic agent than aerosoli zed pcntamidine, empirical therapy should not be initi ated in those patients tolerating trimethoprim-sulphamethoxazole prophylaxis even when the clinical scenerio is highly suggestive of PCP.Nevertheless, the study is extremely use ful and provides obj ective information for empirical treatment initiall y. with bronchoscopy reserved for those who fail to respond appropriately within fi ve days.
Systemic corticosteroids are now accepted as part of standard therapy for patients with PCP and a Pa02 of less than 70 mmHg (7) .If empirical therapy is instituted in such a scenerio it behooves the physician to also prescribe corticosteroids .The advantages have been adequately documented in several tri ab when the diagnosis is certain (8-10).While the study by Tu and colleagues (6) included steroid therapy.they did not factor in potential morbidity.Generally, a limited course of corticosteroids is well tolerated but the potential ex ists for acceleration of respiratory illness when the cause of the disorder is an infecting organism other than P carinii.As well, a history of glucose intolerance will likely influence the prescription of empiri cal therapy and corticosteroids.
Thi s entire debate may be somewhat irrelevant as empirical therapy is the standard of care for many physicians.A survey of 463 respirologists in the United Kingdom questioned manageme nt strategies in patients with HIV.Two hundred and sixty-six phys ici ans responded, with two-th irds choosing empi rical treatment of PCP over immediate fi breoptic bronchoscopy ( 1 l ).
While each case should be indi vidualized, empirical treatment with antibiotics against P rnrinii is a reasonable option under the following scenarios: • Typical radiographic picture in a person with dyspnea and/or nonproductive cough, HIV and a CD4 count less than 200 cells/mm 3 , whether or not the per~on is receiving antiretrovi ral therapy or PCP prophylaxis.
• Previous PCP, typical appearance and the patient is known to tolerate standard anti-PCP medications.
• High clinical suspicion in a patient who refuses bronchoscopy yet desires treat ment, or where bronchoscopy cannot be performed.
Empirical therapy alone should not be initiated when the chest radiograph is normal or demonstrates atypical findings such as nodules, masses, effusions or adenopathy.Finally.prede fined criteria should be established as to when empirical treatment is class ified as a fail ure (eg, five days).Bronchoscopy or other defini tive investigations should then be conducted accordingly.
Pneumocystis carinii pneumonia in HIV history.physical examination.radiology and any of the o ther noninvasive investi gations mentioned.one must also be awa re that there are a variety of d isease states .both infectious and noni nfect io us.that will res ult in dyspnea.bilateral inriltrntes and disturbances in gas exchange .These di so rders include bacteriaL atypical and fu ngal in fections.tuberc ulosis, other mycobaeteria, Kaposi ' s sarcoma.lymphocytic interstitial pne umonia.pulmonary fibrosis , neoplastic disorde rs and congestive heart failu re .As well, atypical manifestations or PCP may occur.Fo•r example.an upper lobe pattern of intersti tial d isease in patients who have received aerosoli zed pcnta m idi ne may occur.
(5)of al I causes.T he likelihood of PC P in the patient with a CD4 count from 100 to 500 cclls/111111 3 is approximately :?.SCI! without and 22'/cwith an1iviral and pneumllL')'Stis prophylaxis (3) .With a CD4 count exceeding 500 cells/mm~.thechance of PCP is extremely low whether or not the patient recei vcs o ther the rapy.investigativetechniquesstudied.suchas a low di ffusion rnpaci ty.arteri al oxygen desaturation wi1h exe rc ise and gallillln scanning.arcquitesensitive hut nonspecil•ic .One study has suggested that the presence of mouth lesions (hairy le ucoplak ia or o ral canclidiasis) and an L'levatL'd nythroL'yte ~cdimentation rate may also raise clinical su spicion(5).Eve n with the information gained rrom a cumhi nation of Can Respir J Vol 1 No 1 Spring 1994