Successful Treatment of Pneumocystis

~Carinii andn~u~~~°"~N and

Nocardia Ast«v~d~

Renal Transplant Patient

MICHAEL L. COx~, M .D .*EARLE B. WE!SS. M .D .ANTHONY P. MONACO, M .D .

Boston, Massachusetts

From the Lung Station (Tufts), Tufts Medi-cal Service, Boston City Hospital, Boston,Massachusetts and Department of Surgery,Harvard Medical Snhoo!, and the Trans-plant Division, Sears Surgical Laboratory,Boston City Hospital, Boston Massachu-setts. Requests for reoNs should be a?dressed to or. Earle B. Weiss, Lung Sta-tion (Tufts), Boston City Hospital, 818Harrison Avenue, Boston, Massachusetts02118. Manuscript received February IQ1970 .

~Present address : Pulmonary Service,Salem Hospital, Salem, Massachusetts01870

Volume 50, February 1971

Asuccessfully treated case of Pneumocystis carinill pneumonia ina renal transplant patient is described, the diagnosis being con-firmed by percutaneous needle biopsy . Treatment with pentami-dine isethionate, 4 mg/kg for 14 days, was successful, with no

adverse effects on the transplanted kidney. In addition, Nocardia

asteroides was holaNd from be sputum, and was successfullytreated with sulfisoxazole. The patient remains we!l after ten

Percutaneous needle biopsy of the lung should be employedpromptly in such cases when conventional measures fail to estab!ishthe diagnosis.

Recent attention has been directed to the increasing Kcidence ofopportunistic infections in patients whose defense mechanismshave been altered by immunosuppressive, adrenal corticosteroidand antimetabolite thempy, by neoplastic diseases or by a de-ficiency in gamma globulin [V4l . The data of HM [5] revealed thatamong forty-four renal transplant patients who died twenty-fivedaysor more after surgery, death was clearly related to infection in 86per cent. The responsible organisms were considered, for the mostpart, unusual ; Nocardia, Aspergillus, Candida, gram-negative bac-teria, Histoplasma and Pneumocystis carinii .In many instonoen, these opportunistic organisms may be na'

oovemb!ofoomoputum,b!oodorp!eura!f!uid ; however, a significantnumber of cases remain undetected by these meonn, and many ofthese treatable infections are recognized only at postmortemstudy. For example, Rifkind [4] observed in an autopsy series ofrenal transplant patients treated with immunosuppressive therapythat of fourteen patients with pulmonary fungal involvement, ap-propriate sputum cultures revealed the offending fungus in onlysix (43 per cent) . The key to oumival in these subjects is prompt,accurate antemortern diagnosis, thus permitting rapid institutionof specific therapy . When conventional measures fail to establishthe pulmonary pathogen, lung biopsy should be performedpromptly. As this case will emphasize, a percutaneous needlebiopsy of the lung can provide a rapid, relatively safe modality forestablishing an etiology in these critically ill patients .Pneumocystis carinii pneumonia, formerly considered a disease

solely of premature or debilitated infants, is now documented to bean &creasing infectious problem in older children and adults undertreatment for hematopoietic or lymphoreticular maUgnanciea, re-ceiving immunosuppressive therapy after renal transplantation orin those with gamma globulin abnormalities [6-21] . Similarly, No-

269

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PNEUMOCYSTIS CA 11 AND NOCARDIOSIS-COHEN ET AL .

DAYS

CLINICAL

AND

LABORATORY

FINDINGS

RANTIMICROBIAL

6

75

8

IMLw2 .0

P

P00" mmHgPIC 02 mmHg

SUN mg'/

PENTAMIDINE4 -g/Kg/day

PENICILLIN

F jwe L Scheme of dKical, laboratory and therapeutic data . See text .

cardia asten~des appears to be occu/hng more fre-quently, primarily in patients debilitated by otherdiseases, and especially in those who are receivinglarge doses of corticosteroids [22-261 .We present a successfully treated case of histo-

logically d!agnosed Pneumocystis carinii pneumoniainarenal transplant padentThadiagnosis wasomn'firmed by percutaneous needle biopsy, and the pa-tient was treated with pentamidine isethionate . Thecc- rse was additionally interesting due to the simu!-

Figvr 2. Chest roentgenogram obtained on admission,e"aUrig a dense mfiluate in the lower lobe of Me WgAlung and minor right apical changes .

taneous recovery of Nocardia asteroides frosputum. This was also successfully treated .

CASE REPORT

A forty'nino year old man, a purchasing agent,admitted to the Boston City Hospital on February196% with complaints of fever, **uknmss, coughyellow sputum, and marked shortness of breath .

Bi!atural staghorn calculi and pyelonephritisdiagnosed in 190 . Renal failure developed inand the patent had been maintained on intermittenthemodialysis. A bilateral nephrectomy was performedin April 1968 eand on December 12, 1968, he receiveda cadaveric renal transplant ImmunosuppressNetherapy (Figure 1) consisted of prednisone, Imuranantilymphocytic serum and local radiation tmthmtrans-planted kidney. After the transplantation, he was treatedsuccessfully for an episode of acute tubular necrosiswith intermittent hemodialysis, and for a Serratia baotamr!a with kanamycin. He was discharged on the fif-tieth day after the transplant (February 1, 1969) with ablood urea nitrogen of 46 mg/100 m!, and a screatinine level of 1 .8 mg/100 mi .

Two weeks after discharge (February 15, 1969) heexperienced a dry cough followed by progressive fe`tigueq temperatures of 100 1 to 1031F, and productionof yellow-green sputum . Just prior to admission,dyspnea developed with minimal exertion . He had beena cigarette smoker until six years previously but deniedsymptoms of pulmonary disease . No occupational orgeographic pulmonary exposure could be established,and a chest roentgenogram obtained in December 1968was clear except for old right costophrenic angle b!unt^

o

e

Physical examination on admission revealed a mid-dle-aged man who appeared acutely ill, chronically

wasted and profoundly weak . The temperature was

101 0 F, pulse rate 120/minute, blood pressure 140/90mm Hg and respiratory rate 24 breaths/minute, The

skin was pa}e, and there was no cyanosis . Chest ex-

amination revealed dullness, decreased breath soundsand rales over the base and mid-axillary area of theright lung. The transplanted kidney, palpable in theright lower quadrant, was nontender, and the bilateralflank incisions were healed .

The hematocrit was 22 per cent, and the white blood

cell count was 11,800/cu mm, Examination of the urinerevealed 1+ glycosuria and 600 mg protein/L . TheWine sediment contained 2+ white blood cells andbacteria, which on culture yielded Serratia >100,000colonies/cu mi . The blood urea nitrogen was 52 mg/100 m!, creatinine 2 .Q /ng/l0D mi, serum sodium 120mEq/L, potassium 4.7 mEq/L, chloride 108 mEq/L,

carbon dioxide combining power 10.5 mEq/L, calcium7 .Omg/IOOm!8 phosphorus 2 .7 mg/100 mi, randomblood sugar 296 mg/100 m! . The serum total proteinwas 5.6 gm/100 ml (albumin 2 .7 gm), serum glutamicoxalacetic transaminase 32 units and uric acid 4 .2mg/100 m! .

!nitial blood cultures grew D . pneumococcus, type17 . /k gram stain of the sputum revealed gram-positive

dip!noocoi, while sputum culture grew B . pyocaneus,Staph aureus, group B streptococci with beta hemolysis,D. pneumococci and Neisseria flava .

The chest roentgenogram obtained on admissionrevealed a diffuse alveolar type of infiltration in thelower lobe of the right lung and minimal infiltrates inthe apioal portion of the upper lobe of the right lung

(Figure 2). The left lung appeared essentially clear .Based upon the b!ood, sputum and urine cu!tureu, peni-cillin (6 million units/day), nafcillin and gentamycinwere administered . Over the next four days the patientcontinued to exhibit daily fever spikes, the respiratoryrate rising to 40/minute and pulse rate to 124/minute .On the fourth hoopital day bi!aterml rales were noted,

and on the next day there was atrial flutter with aventricular rate of 156/minute . A chest roentgenogramat this time revealed progression of the infiltrates inthe right !ung, and also diffuse infiltrate in the left lung(Figure 3) .

On Mach 3, 1969, physical examination revealedprofound dyspneu, cyanosis and Ane crepitant ralesover all !ung Adds . The sputum showed gram-positive

branching filamentous organisms that were in partacid-fast (Figure 4) . The organisms were - consistentwith Nocardia (subsequently documented as N . aster'

nidoa) for which 10 gm/day of Gantrisin was adminis-tered . While breathing mom a ir . an arterial pH was7 .42, Po0 u 64mm Fig, and PaCO2 19 .5 mm Hg. Despitethe recovery of Nocardia and pneumococci, the clinicalsetting also suggested P . carinii pneumonia . The intra'

Volume 50, February 1971

PNEUMOCYSTIS mm/wnmvowoCAnmOS/S-COxEN ET AL .

Figure 3. Portable chest roentgeno gram obtained at timeof percutaneous lung biopsy revealing infiltrates in them id-zone of both lungs and in the lower lobe of the rig ht

Figure 4 . Gram stain of representative sputurn specimen .Gram-positive, branching, filamentous fungi documentedto be Nocardia asteroides are clearly demonstrated .Original magnification X 1,0M

271

PNEUMOCYSTIS CARINII AwoNOCARDIoam-oOHsmET m-

Figure 5. Toluidine blue stain of tissue imprint obtainedfrom percutaneous lung biopsy. P . carinii cysts appear asdark round bodies. An internal structure can be seenwithin some cysts . Original magnification X 1,000 .

muscular administration of pentamidine isethionate, 4mg/kg, was initiated ; the following morning a percu-taneous pulmonary needle biopsy of the lower lobe ofthe right lung was performed without complications . Acore of grey-white tissue, 1 mm by I cm was obtained .Touch imprints of this material, stained with toluidineblue and methenamine silver, revealed organisms con-sistent with P. carinii (Figure 5) . Gram otain, acid-fast stain and crystal violet stain of the imprint revealedno other oragnisms . Subsequent bacterial and fungalcultures were sterile . Examination of the lung biopsyspecimen revealed chronic inflammation, fibrosis andfoamy macrophages with no evidence of pneumocystisor Nocardia .

The following day the atrial flutter was convertedelectrically. The fov*r, tachypnea and tachycardia per-sisted for another four days, and the PaO, decreased to56 mm Hg. By the fifth day of pentamidine and eu!f^isoxmzo|a therapy o!inioal improvement occurred . Thepatient became afebrile, respirations fell to 20/minute .The vital signs remained normal thereafter, and thechest film showed clearing . By March 20, 1969,NNocardia was no longer seen in the sputum and theGantrisin dosage was decreased to 6 gm /day. By March

2 7 2

24 he was clinically wa!, the roentgenogram showedmarked c1aahng ' the R"02 was 75 mm Hg, and a forcedvhul capacity was 2.69 L (58 per cent of predicted) .The patent was discharged on the following medica-tions: prednisone (now tapered to 22 mg/day), Imuran50 mg/day (which had been discontinued during hisacute illness) and Gantrisin 6 gm/day .

During the patient's fourteen days of pentamidinetreatment his renal functions were carefully monitored .The urine volume, osmolality, sodium and potassiumremained unchangmd. There was no glucosuria, no sig-nificant proteinuria, and the sediment revealed only 4 or5 white cells. The blood urea nitrogen ranged between30 and 40 mg/100 mi and the creatinine 1 .6 and 2.6mg/l00m! .

Since discharge, the patient's condition has im-proved progressively . There has been no sputum pro-duction, thadyxpnma has resolved, the chest roentgeno-gram remains essentially clear, and the vital capacityhas risen to3.5G L (78 per cent of predicted) .

The transplanted kidney continues to function ade-quately; the sediment remains banign, the urine cul-tures are ateri!o, the blood urea nitrogen ranges be-tween 40 and 50 mg/100 mi, creatinine 1 .5 and 1 .8mg/100 ml, and the creatinine clearance is 70 mI/mm .ute. The patient was last seen on January 12, 1970(ten month follow-up) at which time he was found to beclinically well . There were no pathogens on sputum ex-amination, andtheuhoxt roentgenogram remains stable(Figure 6) .

COMMENTS

Our patient presented with nonspecific pulmonarysymptomsofthme weeks' duration . D . pneumoniaewas initially isolated from sputum and blood cultures,and odditionol sputum examinations and culturesconsistently revealed Nocardia, for which penicillinand sulfisoxazole were administered . Because of thepatient's profound dynpnea .taohypnaa, hypoxemiaand rapidly progressive changes as noted onroentgenograms despite this re8im*n, and in theclinical context, P. carinii pneumonia was also sus-pected . A percutaneous pulmonary biopsy, employ-ing a Franklin modification of the Vim-Silvermanneedle, and following the technic described by Krum-holz et al . [27], confirmed this clinical impression .After four days of specific pentamidine therapy,there was dramatic clinical improvement .

PNEUMOCYSTIS CARINII

P. carinii was first clearly recognized as a rat parasiteby Cahniinl9l0 It has been classified as a protozoanof the class Sporozoa. To dato, it has not been cul-tured, nor has a pure antigen been isolated .` Rosyim, ear, in the l92O'sn described a type ofchronic intoratitial pneumonia occurring in infantsthat was associated with large numbers of plasma

cells; and Van der/Neerand Brug [281 in 1942 firstshowed P. carinii in human lung disease . P. cariniipneumonia was then extensively described in theEuropean literature in the 1940's as occurring ph-mahly in premature and debilitated infants Q . Sincethe early reports in the United States [30] and En'dend [K] in l&55 ' this disease has since been recog-nized under the following clirlical circumstances :(1) renal transplant patients receiving immunosup-pressive therapy, (2) hematopoletic and lymphoretic-ular malignancies on adrenol corticosteroids or cy-totoxic agentm, (3) immunoglobulin deficiency states .There are only two well documented cases in adultsin the absence of underlying disease [32,33] . Sub-clinical P . carinii pneumonitis was described by Shel-don [34] who suggested that in the normal host P .carinii infections are of low viru!enca, thus implyingthat host-resistance facto, must be severely com-promised before the parasite can produce clinicaHymanifest disease .Activation of latent colonization has been clearly

demonstrated in animals [17,35] . For example, theorganisms have been found in the lungs of healthyrats and rabb{ta, albeit in very low numbers, becom-ing activated by alteration of the host's resistancewith adrmnul corticosteroids, anti metabolites, anti-microbial or chemotherapeutic agents . These exac-erbations in animals are confined to the lung, whichappears to be the case in man ; the pathology is alsoquite similar . Rooent!y, ho*ever, a case of general-ized P . carinii infection in a patient with severe idio-pathic hypoproteinemia has been described [367,and P. carinii have also been identified in lymphnodes and spleen [37] .The pertinent pathologicfeatures of P . carinii pnew

rnonia include (1) a chronic interstitial pneumonia,(2) prominent alveolar septal cells (cuboidal or flat)and amorphous foamy exudate (which can extendinto the respiratory bronchioles), (3) absence of tis-sue necrosis and a paucity of polymorphonulcearcells, (4) lymphocytic and particularly plasma cellin1erstifiol infiltration, (5) absence of fibrosis, and(6) absent pleural involvement .The 4 x size, spherical intra-alveolar cysts stain

readily with Gomori's methenamine silver or Grawe'smodification of the toluidine blue stain [3A] . We ob-served that tissue imprints revealed many moreorganisms than did fixed sections ; in faot, in ourcase the tissue sections were negative for P . carinii .Other investigators appear to express a similar pref-erence for touch preparations of biopsy material[7 .19'29 .39] .

Rifkind 0] studied arterial blood gas data in five

cases of P. carinii pneumonia . Oxyhemoglobin sat-uration values ranged fmm 915 to 415 per cent, Thepartial pressures of carbon dioxide were normal orslightly low. In another report [321, the pulmonarycompliance was markedly decreased to 0 .02 L/cm

Volume 50, February 1971

PNEUMOCYSTIS CARINII AND NOCARDIOSIS-COHEN ET AL .

Figure 6. Six month follow-up chest roentgenogramshowing resolution of P . carinii infiltrates, appearing es-sentially the same as the pretransplantation film .

H,O (normal 0.2 L/cm H,O). The clinical course ofrelentless progression appears associated with in-creasingly severe hypoxemia . Although unclarifiedat present, the hypoxemia seems to be due to a dif-fusion defect and/or venous to arterial shunting .The clinical presentation of P . carind infections is

often insidious and includes a nonproductive cough,dyspnea, cyanosis and a low grade temperature .Sputum production is not a major feature of thisdisease ; if present, other associated pathogensshould be suspected . With progressive involvement,fever may exhibit a high spiking pattern, severe tachy-pnea and cyanosis may develop, and death fre-quency results from progressive respiratory failure .Lung auscultation often reveals only a few scatteredrales ;' thus a usoful c!inioal observation is the disso-ciation of physical findings, which are sparse, andthe roentgenologic changes, which are gross .

There are no distinctive x-ray patterns of this dis-order. The most common appearance is that of hazy,

with predominant opacification in the perihilar zonesand lung bases. Early roentgenographic findingsmay precede diniuol events. This picture may beconfused with pulmonary edema or other disorderswhich produce a butterfly pattern on roentgeno-grams. Nocardia may rarely produce a similar roent-genologic pattern but should generally not be con-fused with pneumocystisinfections . ~

Diagnosis is established by identifying the proto-zoan either in the lung or its secretions . Since thesepatients do not produce significant sputum, tracheallavage has been advocated as an approach . Ivady

273

PNEUMOCYSTIS CARINII AND NOCARDIOSIS-COHEN ET AL .

et al . [40], basing their views upon vast experiencewith premature and feeble infants, prefer smearsof tracheal mucus obtained by aspiration through alaryngoscope. Using this technic they have identi-fied organisms as early as seven to ten days priorto changes noted on roentgenograms and clinically. .Although P. carinii has been identified in fixed sevtons of hypopharyngeal material recovered from aninfant, most investigators believe that the organ-ism rarely, if ever, appears in the sputum [41] . Be-cause oftheinebi/itytoidentifythmorganisminspu'tum . lung biopsy is recommended to establish thediagnosis. In cases of P . carinii pnnumon!u, openlung biopsy, although an accepted approach, hasbeen reported to be associated with problems com-mencing vvithanesthesiaandoontinuin8throu8hthopostoperative period. In some cases assisted vewti!utiun was required postoperYkely because ofsevere respiratory distress [11,18] . Percutaneous lungbiopsy is an alternative approach, having been suc-cessfully employed in obtaining specimens for or-ganism identification with only minor complicationsNaJjAb To date, we have successfully employedpercutaneous pulmonary needle biopsy in two renaltransplant patients to confirm the presence of P .carinii pneumonia. There were no complicationsother than transient hemoptysis (5 to 10 cc) . Rob-bins [Bb however, mentions aoaa* in which nonde

enomprossab!e pneurnothorax and death followedneedle aspiration of a lung infected with P . carinii .At the present time, our experience parallels that ofmthera, in that percutaneous !ung biopsy is a rapid,useful diagnostic modality with minor morbidity andmortality for problems of d1fuse pneumonopathy[27,43]. This procedure is especially germane in criti-cally Ul patients suspected of having F! carinii pnou'monia.vvhooftonaveponrsurgioa!uandidatos .In the English literature, there are twelve cases of

P. uarin!i pneumonitis, proved at biopsy, in whichthe patients were treated successfully [n7 .lI.l3 .l5,'IG.I8.I9], later deaths being attributed to othercauses . One patient was successfully tweed withhydroxyst!bennidine, another with amphotericin andlarge doses of corticosteroids [13,16] . The other tenpatients received pentamidine is*thionato, a di'amidine with trypanosomicidal activity, found to beeffective in man and animals [44] . Ivady, the firstto use the drug in man (I050), observed that fromthe sixth day of treatment degeneration of the pnewmuoyatis became more and more prominent; by thetenth day, the organisms had almost disinto8natodand thereafter were no longer demonstrable . In in-fants, with a dose of 4 mg/kg over twelve to fourteendaye, the c!iniual effect became apparent four tosix days after the initial injootiun, the on, side ef-fects being "occasional erythrocyturia and anemia .',The mortality rate decreased from 50 to 3 per cent

2 7 4

The drug, administered intramuscularly, occa-sionally causes pain at the injection site, and tissueCough has been reported [7] . Nausea and vomiting,dizziness, hypotension, tachycardia and hypogly-cemia have also been described. Megaloblastic bonemarrow changes, possibly related to an antifolateeffect of the druQ, have been described [8y Of par-ticular concern to our patient with mnal transplan-tation are the recent reports of possible nephrotoxi-city . DeVita et al . [6] reported a case of apparent renaltubular dysfunction, questionably secondary to dou-bling thmdomeofpantemidinmfortwodeys . In a sec-ond case the patient experienced one day of oliguriawith full recovery ; however, nephrotoxic antbiotcsmay have been added factors . Our patent received4 mg/kg intramuscularly for fourteen days withoutrenel injury, as measured by daily urine output, urineelectrolytes, urine sediment and blood urea nitrogenand creatinine levels .

Of the twelve surviving patients described in the!iteratura, concomitant with pentamidine adminis-tration, two patients were treated successfully whilereceiving larger doses of steroids, three patientswere treated successfully while on a decreasing ste-roid schedule. At the present time there is no firmevidence that it is necessary to increase, decreaseor discontinue the administration of corticosteroidsin order to treat P . carinii pneumonia . This point willrequire further clarification . `

NOCARDIA

This genus of fungi typically presents as gram-posi-tive, partially acid-fast, filamentous appearing formswith fine branching hyphae that tend to break up intobacillary or onroal fragments . These grow aerobi-cally on routine culture medium, distinguishing itfrom other anaerobic species . Worldwide in distribu-tion, , Nocardia appears to colonize man directly viathe inhalation route . Most investigators contend thatNocardia is a saprophyte in man, thus its presencein sputum indicates ongoing pathogenicity requiringappropriate therapy [23,45,46] . Nocardia asteroidesis the most common species infecting man, mani-festing primarily as a brnnohopu!monary dieorder,although systemic dissemination is an added com-plication . Thoooursemeybeoitharaoutoorohroniu,localized or disseminated, and may resemble acutepneumonitis, chronic tuberculosis, lung abscess orneoplasm .Prior to sulfonamide therapy the mortality rate

was estimated at about 75 per cent [22b at presentthe over-all mortality is cited at about 50 per cent .This value may be somewhat misleading in that no-cardiosis usually occurs in those who are seriouslyill with other diseases, especially in those receivinglarge doses of adronouortical steroids [22 .24 .2S .45,47-49] . The inddence of nocardiosis appears to beincreasing, perhaps attributable to the improved

The American Journa of Medicine

survival of patients with serious undto the increased use of adrenal corticosteroids andto inveaWng diagnostic acumen . Sulfonamides arecurrently the drugs of choice [50], first successfullyadministered in 1944 by Benbow et al . [51] . Straussand associates [52] in 1951 ddemonstrated with an!noalprotection studies that sodium sulfadiazine impartedalmost 100 per cent protection to infected mice . Su!'fadiozin* has been the most frequently employedsulfonamide, provided in dosages to attain swumconcentrations of Oto 12 mg/100 ml [22] . Successfultreatment has been reported with sulfisoxazole [22,53], sulfamethoxine [22], sulfanilamide [53] and triplesulfate [53,54] . Thus, any of the available sulfon-

amides yielding adequate and sustained blood con-centrations appeerequa!!y effective by present cri-teria. Sulfa drugs should be continued for at leasttwo or three months, and if chronic disease persists,for one year or longer . Sulfisoxazole (Gantrisin) israpidly excreted, relatively highly soluble in urine,only infrequently produces honnutuhm or crystal-luria (02toO.3 per cent) and is associated with a low

EREIN

Murray JF, RmegelimHF, Hewitt WL, Latt H, MoVickaro ' Rasmussen AF, Rigler LG : The U]C.L~.!monuepurtmental conference-opportunistic pul-monary in/entinns . Ann Intern Med 65 : 566, 1966 .

HHutter RVP, Collins HS : The occurrence of oppor-tunistic fungus infections in a cancer hospital .Lab /nveso11 : 1035 . 1962 .

Hill R8 Jr, Rowlands DT Jr, Rifkind D : Infectiouspulmonary disease in patients receiving immuno-suppressive therapy for organ transplantation .New eng J Med 271 : 1021, 1964,

Rifkind D, Marchioro TL, Schneck SA, Hill RB Jr :Systemic fungal infections complicating renaltransplantation and immunosuppressive therapy .Amm,J Med 43: 28, 1967 .

splantation . Amer J Mad 42 : 327, 1967 .DeVita VT, Emmer M, Levine A, Jacobs B, Beard C :

Pneumocystis carinii pneumonia . New Eng J Med280:287 ' 1969 .

Lillehei JP, FunkeJL . DmgmCW, Sharp HL, BurkeBA: Pneumocystis carinii pneumonia . JAMA 206 :5g6'1n%inmV' FansTQ Hill RB Jr: Pneumocystis carinii

pneumonia. Ann Intern Med 65 : 943,1966 .pneu-9 . Esterly JA, Warner NE : Pneumocystis carinii pneu-

monia. ArchPath (Chicago) 80 : 433, 1965 .Voge!CL ' Cvhen MH, Powell RD, DoYiteVT: Pneumo-

cystis cahnii pneumonia . Ann Intern Med 68 : 97,

11 . Smith E, Gaspar IA : Pentamidine treatment ofpneumocystis carinii pneumonia in an adult withlymphatic leukemia . AmerJMad44: §26'I968 .

12 . Mulligan WJ, Krause FD, Momin8starYY . Baum GL :

10 .

Volume 50, February 1971

'

PNEUMOCYSTIS CARINII AND NOCARDIOSIS-COHEN ET AL .

risk of anuria [55] . We therefore prefer sulfisoxazolein the hope of minimizing any added insult to trans-plant kidneys .Other antibiotics suggested for treatment of No-

cardia include penicillin [56], penicillin combinedwith streptomycin [57], penicillin and chlortetracy-cline [58], chloramphenicol [5U] and cycloserine [60] .A review of the }iteratune ' however, offers no un-

equivocal criteria as to which antibiotic, if any, shouldbe used in conjunction with sulfonamides .Finally, this case additionally serves to emphasize

that patients with compromised immunologic de-

fense mechanisms may be suspectible to infectionwith more than one "unusual" organism . In a reviewof twenty-three deaths after transplantation, 83 percent of the patients with systemic fungal infectionshad a concomitant infection, usually pneumonia orsepticemia ; of these, five were due to P . carinii, theothers being bacterial [4] . Cytornegalovirus vas alsofrequently observed in the postmortem lung exam-ination in this series, but was considered not to be adirect cause of death .

:ES

Pneumocystis carinli infestatio1017,1968 .

13. Schultz JC, Ross SW, Abernathy RS : DiagnosisPneumocystis rarinil pneumonia in an adult withsurvival, Amer Rev Resp Dis 93 : 943, 1966 .ert CF, Fordham CC, Benson WR: Death resulting

from Pneumocystis carinii pneumonia in an adult.Arch Intern Med (Chicago) 112 : 56: 1963 .

BEinzig S, Hong R, Sharp'HL: Successful treatment ofPneumocystis carinii in an immunologically defi-cient acute lymphatic leukemia patient. Cancer 23 :658,1969 .

Moore DL, CurnohwnCE. Mills SD, Burgert EO Jr :Pneumocystis carinii pneumonitis complicatingleukemia. Mayo Clinic Proc 44 : 162, 1969 .

RunhinJ ' Remington JS: The compromised host andinfection-1 . Pneumocystis carinii pneumonia .JAMA 202: 1070 ' 1967 .

18 . Robbins JB : Pneumocystis carinii pneumonitis-aPedik Resk 131, IS67 .

1!l Marshall WC, Weston HJ, Bodian M : Pneumocystishypogamma-carinii pneumonia and congenital hypogamma-

globulinemia . ArchDis Child 39: 18, 1964 20. Patterson JH, Lindsey IL, Edwards ES, Logan W

Jr: Pneumocystis carinii pneumonia and ahost resistance: treatment of one patient withpentamidine isethionate . Pediatrics 38 : 388, 1966 .

21, Post C, Dutz W, Nasarian 1 : Endemic Pneumocystiscarinii pneumonia in South Iran . Arch Dis Childag:ss.lg6? '

22. Murray JF, Finegold 0N . Froman S, Will DW : Thechanging spectrum of nocardiosis . Amer Rev RespDis 83 : 315, 1961 .

23 . Neu HC, Silva M, Hazen E, Rose

io MadJ6

SH: Necrotiz-

Ing nocardial pneumonitis . Ann Intern Med 66:' l967

Hathaway BM, Mason KN : Nocardiosis . Ame J Med32:903,1962 .

Beeson PB : Nocardiosis, as a complication of pul-nary alveolar proteinosis . Ann Intern Med 60 :,1964 .

Larsen MC Diamond HD, Collins HS: Nocardia as-teroides infection . Arch Intern Med 103 : 712,1959 .

ease. Amo!ntemMedI08 : 173, 1961 .

cystis carinii in lymph nodes and spleen . ArchPath 88: 175, 1969 .

ChalvardyanAM.Grmwe LA: A new procedure for theidentification of Pneumocystis carinij cysts intissue sections and smears . J Clin Path 16: 383,1963 .

carinii in hypopharyogaol material . New Eng JMed 267: 926, 1962 .

Jacobs JB, Vogel C, Powell RD, DeVita VT : Needlebiopsy in Pneumocystis carinii pneumonia . Radi-ologyology 93 : 525, 1969 .

OCYSTIS CARINII AND NOCARDIOSIS-COHEN ET AL.

4 3, YoomansCRJr, Middlet nJK, Derrick JR, MorettinLB, Assor D: Percutaneous needle biopsy of helung for diffuse poenohvmal disease . Dis Chest54: 25, 1968.

44, Frenkel JR, Good JK, Shultz JA: Latent Pneumocystisinfection of rats, relapse, and chemotherapy. LabInvest 158: 1559, 1966.

45. Raich RA, Casey F, Hall WH : Pulmonary and cutane-ous nocardiosis. Amer Rev Resp Dis 83 : 505,1961 .

Shuster M, Klein MM, phbonH[, Kozub W : Brainabscess due to nocardia . Arch Intern Med 120 :610,1967,

Saltzman HA, Chick EW, Conant NF: Nocardiosis asa complication of other diseases, Lab Invest 11 :IllO ' Ig62 .

Carlsen ET, Hill RB Jr, Rowlands DT Jr: Nocardiosisand pulmonary alveolar proteinosis. Ann Internmeu60: 275, 1954

AndnolmVT, Ballas M, Wilson GL : The associatinocardiosis and pulmonary alveolar proteinosis .

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