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Chronic Pseudomonas aeruginosa Pneumonia in a Normal Adult
Chronic Pseudomonas aeruginosa Pneumonia in a Norm al Adult* Repor t of a Case D. ROSE. M.D. Wood. Wisconsin
HAROL D
T
H E INCIDE NCE OF PNEUM ONIA CAUSE D
by the common gram-negative bacilli has increased in the last decade.' Members of the Klebs iella, Escherichia, Proteus, Pseudomonas, and Bacteroides genera are the causative agents in approximately 4 per cent of all pneumonias seen in a large hospital today,' Although this changing pattern of pneum onia can be attributed to many factors, several recent studies have emphasized the importance of serious underlying diseas e in predisposing to gramnegative bacillary pneum onia in man.r" Chronic pulmonary disease, diabetes, alcoholism, and malignancy are known to impair the resistance of the host to bacterial invasion. Concurrently, the presence ofsuch diseases in the host may require the administration of several forms of therapy that further increase the risk of infection. Finally, if hospitalization becomes necessary, there will be the added risk of exposing the susceptible host to the nosoc omial flora of gram-negative bacilli. It should not be surprising that most cases of gram-negative bacillary pneumonia are now acquired as terminal infections in the hospital environment. 1.a 04 The purpose of this report is to describe in detail the circumstances under which fatal Pseudomonas aeruginosa pneumonia appea red in an otherwise healthy middle-aged man. CASE REPORT
A 43-year-old, white painter was in good health until May of 1964 when he developed a sore throat, hoarseness, and a cough productive of small amounts of yellow-green sputum, He consulted a private physician who made a diagnosis of acute bronchitis. Intramu scular injections of procaine penicillin-G were administered daily without improvement. After five days, the penicillin was discontinued and a two-week course of *From the Medical Service, Veterans Administration Center.
tetracycline (Achromycin V) was prescribed. A severe stomati tis ensued with difficulty in mastication, dysphagia, and a 20-pound weight loss. First Hospita l Admissi on: He was admitted to a private hospital on July 27, 1964 for evaluation of cough and stomatitis. His occupation as a house painter did not entail unusual exposure to noxious fumes or sprays. There was no history of vomitin g or excessive alcoholic intake, The results of physical examination were normal, except for diffuse inflammation and dryness of the oral mucous membranes. Candida albicans was isolated from a culture of the tongue. Sputum cultures (3x) yielded Candida albicans and Pseudo monas aeruginosa (few colonies to a heavy growth ), A chest roentgenogram was normal. The only medicat ion the patient received was a nystatin (Mycostatin) suspension administered four times daily, to be held in his mouth and swallowed. Although the patient's cough persisted, the stomati tis improved and he was discharged after ten days of hospitalization, Second Hospita l Admission: He was adminc d to a second private hospital on August 17, 1964because of shortness of breath and wheezing of seven days' duration. Physical examination revealed an acutely ill white man who was dyspneic at rest. The temperature was 101°F (38.3°C). Expirat ory wheezes and rhonchi were audible over both lungs. Sputum cultures (7x) yielded mixed flora with a predominance of Pseudomonas aeruginosa (moder ate to heavy growth), The admission chest roentgenogram was normal. During the first three weeks of hospitalization, he had a daily tempera ture of 101°F (38.3°) that failed to respond to 600,000 units of procaine penicillin-G administered intramuscularly every 12 hours. He became afebrile while receiving oral demethyl chlortetracycline (Dedom ycin), 150mg every six hours, and intramuscular colistimethate (Colym ycin), 150 mg every 12 hours. Because of a poor clinical response to antibiotic therapy, bronchodilating drugs, and expectorants, a fivelobe bronchogram was performed on September 4, 1964 and was interpreted as normal. Subsequent courses of oral chloramphenicol (Chloromyce tin), 250 mg every six hours, and oral erythromycin (I1osone), 250 mg every s~x hours, were administered empirically without Improvement in symptoms. During the last four weeks of hospitalization, he received inhalation therapy
643
for the firs t ti sulfate (1 m me in the form of st re l four times da of 50 m g /m l solution ptomycin ) nebulized ily by in te rm Cultures of it te n t positi the ve pressure. for Pseudom sputum were persiste nt on ly positive as ae rugino roentgenogra ms disclose s4. and repeated ches d t linear and p trations of bo atchy infil· th lungs. In spite of wor in the roen sening n o te tgen d improved su ograms of the chest, his dyspnea fficiently to a ll o w disc eight weeks harge af te r of Third Hospi hospitalization. days at hom tal Admission: D u ri n g the n ex t 11 e, he experi en y w s of co ughing, dysp ced increasing parox ne necessitated a, a n d whe re on October admission to the priv ezing th at ate hospital 24 amination w , 1964. T h e results of physical exere unchange d ture of 100° F (3 7 .8 ° C ). except for a te m p er aS p u tu m cult mixed flora ur w aeruginosll (mith a predominance of Psees yielded udomonas o d er at e to he tion to the pr eviously desc avy g ro w th ). In ad d iri chest roentg enogram re bed abnormalities, the ve area of infi ltration in th aled a m o re discrete e lower lobe lung. of the le ft T h e admissi on diagnosis and b il a te was chronic ra bronchitis cance of th l bronchopneumonia. e repeated T h e signifiisolation of Ileruginosll fr Pse om the spu tum was no udomo1l4$ time. T h er ap t clear at th y was initia e ted w it h 3 per cent so ml luti nebulized th on (2.5 m g /m l) of po of a .25 ree times da ly ily by in te rm myxin B tive pressure . For the fi it te n t posirst oral chloram phenicol (C five days, he received hloromycetin ) in a dose JULY
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m g j1 0 0 Olytod Sug tein elelectr o e ValUes Were S er u m p ro . ph al to ct rm C o 9.06 sis reVealed n e p ro te in of ,; l ta 'nI, ~.rtt Per 0 ml, al b u m ' a to gm p e r 100 l~ct' Ith tnod erate elevati rn 3.83a c h globulin 1lI~ ~Oll. J\n.l111muUoelec On of e di losed n o r. horesis sc J<', 11l1ll1un oP tr . ns li bu glO lor llI lilll sle;...: tests s 1 fixation'te.st ;,J b last° ll ty co ' a n d Com ~enta d opl"'ftPOe _ st "l"01ll lO hi ld S, cc I SI S co S ,n . e -m 1lell'.. rc\'eosj,s were n egatlY S s were o"tI m Culture ~ t fOr Ii U P b' ( co nd . tu Slrell A re i. g n lm )u cu se h st dUt ~h, p p U Wa P O s iteriv e ' rns 25 mm of ruIth Sput berclaho.-'. W w s re r tu fo ul e C iv lt at ~l ere n eg d a Pite baCilli . ~Ot1tine s lt u re s yielde a ,re Cult re o f P.relldPUtunm cu Uginosa an d U T 0 ~olll/J(ed 8 with a I'01nO '!S ae e o f Pseudo. ~ nfl.rC4etu 61r?1loSfl• A. b P edOllUnanc examination tis. e elllb IS, 1964 :C~oscoPic ic bronchi~r ron qlt/'; PseUdo US ino ea ed ch ?ltas ael'ttg sa a n d Stapkywcocc l e er w s e~ m ia \va o ch fr on d te br of llSola SlerjShltJgs• 1J d CUltur anadcu lt.u re oO lt u re were es b \ cu J . le Ie ?' , ur i"·,'ltl OUe ar ro w ex a . Wed m in O sh m » d no lYeloi asp'ra tr: lasia n U lla u lt u re of the rp pe hy te ' and c V. w s Sterile. t.:ls etl.tilat: lunction d te ri al bl oo ill allalYsi ry fO rt n ed o ~ e ~ a n d ar 1964- were I, o~;rpre~ds: ers cOmpatibI .c em b erdera te airway m~ ll io h Ct lt Uta ~U faUe .w ht ygen sat. ig ox sl .. al A ri li te In ar ' 01 ~1l fO e~ eX ' )8 1l W dl1fusio O • problem """ -
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PNEUMON
IA
use, pa tc hy revealed diff ct area of m ra og en tg in en st s w it h a di o f the le ft _ Ches~ ro be of both lung ~filtrat1ons filtration in the lower lo in d se ea mcr ce of . e significan lu n g (F ig 2) mission, th as aeruginosa ad f o e m At the ti Pseudomon d. In view te d isolation of the re p ea te tu m was n o t apprecia timicrobial u an sp e th um tr m ec o sp fr d a ro b ered a "sec ious of the prev organism w a s consid at ed in the e ic therapy, th er " an d was n o t im pl , the predly ad e. According o n d ar y in v of his diseas hdrawn, antimicrobials is es en og th it pa s gradually w th e t diagnostic studie nisone was ed fu r nu d ti on an sc d, di el were w it hh ed. T h e prednisone was g day, the in m were perfor 4-, 1964. On the follow is temperaH er b r. em ve fe ec D of on a recurrence F (38.3C) an d 1030F p a ti en t h a d tw e e n 101° ainder of hospitalizae b ture was rem mplained of il y lor the (3 9 .4 ·C ) da e onset of fever, h e co a an d reth n ng d y sp e tion. With ess, increasi g at the bedside. A kn ea w ed sittin m a rk ac ti vi ty to mg adminis yxin B, 25 was started st ri ct ed his m ly po of se s, five-day cour cularly every six hour effect on his us te re d intram 18, 1964 and h ad no nsidered a co er on Decemb . A lt ho ug h h e was sy was perse op clinical cour risk, an open lu n g bi December p o o r surgical r general anesthesia on basilar segr formed unde superior and posterio m an d rubhe fir T e . er 64 w 19 be , 8 lo 2 easuring up e le ft lower ments of th tency. Small nodules m throughout is ed ns bery in co diameter were pa lp at ic secin . Microscop to 1 em the left lung from the medial f o er d n ai tained the rem discl~ ge biopsy ob tions of a wed t of the le h upp~r I ?h sllpe~lm It en W gm s n Jingular se specific, pneumcm suppuratIon: n. chronic, no flammation and focal d Gomorl in an posed acute a d d ·S ch iR , ultures for , periodic C en s. ls ee sm ni -N ga hI Zie no microor ruses were. negative. ed al ve re stains and vi was r~gmDsa ast bacilli, fungi, acid-f th of Pseudomonas Qe bIOpSy specow from the A heavy gr p u re culture recovered in biopsy. to the lung n tio imen. ac re e vers December He h ad no aderapy was restarted on e, 25 mg ut th ro B P ol ym yx in tramuscular 1 ml o f a th by the in , 30, 1964, bo s, and by inhalation times da!1y ur every six ho g jm l) nebulized four was mamm e 0 (1 pressure. H solution etent positive ereafter with no appr it rm te in by th ic ph en ra m gi og tgen is re tained on th on the clinical or roen 65, h e had 19 , ct ciable effe iJJness. On Ja n u ar y 13 a n ? died course of his t of massive hem?pt-rm (FIg 1). n se io n at o It an ab ru p t rous efforts at resuSC abnor· e th revealed sy despite vigo op cr ne sy at y stem. Examination m it ed to the respirator partially li h it be was filled w was dif. malities to e ronchial tree The tracheob and the mucosal surfacere free of w d oo es bl ac d sp te l ra clot ed. The pleu cut surfaces fusely inflam s were firm and the e a t te re d ng lu ma. S fluid. T h e red parenchy ere many small his ay gr a disclosed hyma w the p a re n c throughout
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HAROL D D. ROSE
areas of induration of yellowish discoloration. In the right lower lobe there was a large area of necrosis and cavitation that measured 6 x 10 em in diameter and contained clotted blood. In the left lower lobe there was a similar cavity that measured 3 x 3 cm in diameter. This cavity communicated with a bronchus and had eroded into a pulmonary vein. Frank pus was not encountered in either lung. Microscopic sections of the lungs revealed occasional areas of fibrosis and infiltration with lymphocytes that had replaced the normal alveolar pattern. More striking, however, were areas of severe necrosis occupied by innumerable poly. morphonuclear leukocytes. The walls of the small bronchi and blood vessels that lay adjacent to these microabscesses were infiltrated with acute inflammatory cells. Several small arteries were occluded by a thrombus. In other areas, the alveolar septae were intact and red blood cells were present within the alveoli. The results of special tissue stains and cultures were again negative. A routine culture of both lungs yielded PseudomOll6s aeruginosa in pure culture; 0.5 ml of a ~4.hour old subculture of the organism was in[ected subcutaneously into the abdominal waH of a guinea pig and produced a 3 em in diameter ulceration after 72 hours.
the ~ocal mecha nisms by which the lo",e( respiratory tract clears itself f b ,.;s,. ' H ow~ver, It would appear that 0theiraete.· majot role . IS to alter the systemic d ef ense meo_I.,' arusrns of the host and allow th ftY negativ e bacilli to implan t in es ' pu legt1Lar mon l t Issue.
The common gram-negative bacilli have a low degree of pathogenicity for human pulmonary tissue. If these organisms are to cause pneumonia, they must be able to enter the lower respiratory tract in sufficient numbers, and have their tissue invasiveness enhanced by factors in the host that impair resistance to infection. Forem ost among these many factors is the presence of serious underlying disease in the host. In 1960 ~n.eeland and Pri~e3 reported an increasin~ incidence of terminal gram-negative bacillary pneumonia occurring in patients with such diseases as malignancy hepatic failure ' , u~mla, apoplexy, and conge stive heart failure. Lepper' noted a similar trend in patients who developed pneumonia in a general hospit al from Januar y 1960 to March 1962. More recently Tillotson and L emer1 reporte ' d their experie nces with 38 cases of gram-negative bacillary pneumonia ~een at the Detroit Receiving Hospital dur109 a 12-month period. Thirty-six of their cases h~d serious chronic diseases including alcoholism, congestive heart failure, diabetes, and chronic lung disease. The presence of such diseases in the host may suppress
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Many ~ronically ill patients will eve~' tu~lly req~lre a form of therapy for th el! prImar y dlSo~der ~hat is known to further ~ncre~se. the risk of mfection. Corticosteroi~' Irradiation, and cance r chemothe apelltlC drugs may be indicat ed in the man:geJJ1eflt of these patient s and are capable of sur pressing the inflam matory or leukoc ytic response of the host. Proble ms in venule.' tion may arise and necessitate the use of prolonged trache al intuba tion or tracheostomy. The presence of an airway in tit' trachea will not only create a direct co~ munica tion with the enviro nment but ",iU act as a foreign body and facilit ate tlI' colonization of gram-n egative bacilli in tll~ mucosa of the lower respiratory passages, Finally, several recent investi~tions bave defined the hazard associated with the 1l~ of contam inated mecha nical respiratOrsReinar z et al have demo nstrat ed verY clearly that the gram-n egative bacilli are the major contam inants of inhalat ion ther~ apy equipm ent. In contra st to the other common pathogens, t h es e organisms can survive and multiply in a humid environ' ment, If the inhalat ion therap y equipment is not properly decont aminat ed, large nllnl~ bers of gram-n egative bacilli can be aero~ solyzed and carried into the lower respiratory tract of susceptible patients..\lthOllgh these modes of therap y constitute important, advanc ements in the care of the chronicalh ill patient, there is no quesiton that the risk of infection is increased when these agents are administered either alone or in com~ bination, Certainly, the hazar d of cro:s~ infection from the nosoc omial bactenal flora must be kept in mind when such treat· ment is undert aken in the hospital enviro n'
ment, In the patient presented here, the onset of the fatal Pseudo monas pneum onia could
Volume 53. No. 5 May, 1968
CHRONIC
Pseudomonas aeruginosa
not be attributed to any of the above-mentioned factors. A careful clinical and necropsy study failed to disclose the presence of an underlying disease. Although the patient did receive inhalation therapy and corticosteroids, they were both administered after the pulmonary infection was well established. Furthermore, the circumstances under which the illness developed and the isolation of the causative agent from the initial sputum culture are evidence against the infection being hospital acquired. It would appear that the onset of the Pseudomonas pneumonia could be attributed to a single major factor, namely, the administration of "broad spectrum" antibiotics with the subsequent alteration in the bacterial flora of the respiratory tract. The replacement of the susceptible bacterial flora by resistant "opportunistic pathogens" is one of the well-recognized ecologic changes caused by antibiotic therapy. Rogers" and others have emphasized the importance of this selective action of antibiotics in the overall increase in the number of gramnegative bacillary infections seen today. In a postmortem bacteriologic study of pneumonia, Kneeland and Price" also concluded that the introduction of antibiotic therapy ?as played a major role in the increasing Incidence of gram-negative bacillary pneumonia. It should be emphasized again that this study concerned a population of serioU'>1y ill patient'! in whom the antibiotic therapy was but one of several factors that may have predisposed to this type of infection. In contrast, the use of antibiotics in the treatment of ambulatory patients with mild respiratory infections provides an opportunity to evaluate the role of these agents alone in predisposing to gram-negative bacillary pneumonia. As might be anticipated, Weinstein and associates" found Only three cases of pneumonia of all types Complicating the antibiotic treatment of approximately 1,500 patients with otitis media, pharyngitis, or tracheobronchitis. One case each was caused by Pseudomonas aeruginosa, Hemophilus inlluenzae, and an Unknown gram-nep;ative organism. Lep-
PNEUMONIA
per':" studied the same problem in a group of
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HAROLD D. ROSE
very rare. Nev ertheless, the ou tcom present patient demonstrates th e ~n th e occur and indi cates th at earl a~ ~bis can y cllIDCal and bacteriologic re cognition of th e tion is mandato ry if proper tr super~fec eatment IS to be instituted, Rl
!.I1E1l.l!.NCES 1 PIEII.CE, A. K. ., ED M ON SO N, E. K.l!.
'tCltl!.IlSID,
J., Lo
B., MCGEE, G .,
UD O N, R. J. P.: An G. AN SA t!l 'O 'R D, gram-negativanealys1S of factors. predI!tspo ba ci lla ry necrotizing pn slng .to Amer. Rell. Re 2 TI LL OT SO N, s;. Dis., 94-:309, 1966eumonia, J. R. AND LEIlNE'lt, . monias caused by gram-nega. A. M.~ Pn eu i, in , (Balt.), 45 tive baciUi, M ,d · :65, 1966. 3 K. Nl !.E l.A ND , Y • biotics and te ., JR. AND Pa lO l!. , K. .M microbiologicalrmmal pneumonia - post.: Antlm study, A m ". tem 1960. l- Mild., 29or :967, 4 L E ns ». , M. H . rod pulmonar .: Opportunistic gram y infections, atIVe Dis. Ch,n,-neg 1963. 44 : 18, 5 TUWEVALL, G .: Bacteriolo nursing of tra gi ca l as pe ct S,o.nd., 31 cheotomi'Zed patients, s on the 6 ME"P.TZ, J.6J.(Suppl. 154) :91, 1956.Acta M ,d. SC ltA U ll, L. J. R.: A hosp, ita AND MCOLl! .MENT~ l outbreak of Klebsiella pn eu -
in~tion .t';:~~: ·w eontaJ;1lin at ed aeroso k;~ RssP, DIs., l solutions,
moniae from
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ltU-L M. C., 7 McNA1It....1lA B....L~~t~tio. , M. 1. . A ~udy ...NO Tu cl tE B th e Ann. In" ll. , E; bo " ·tal infecto.f . e pa tte rn s ions, OL l ed 66 :4 80 , 1967Sp tJl la& . G 8 PHU"-t:lPS, 1. ' ps eu do . Ol S NOEll. ,,·ed .• • AN D tl1 Pt i.o n11 .1l n ..• ae ru gm os a cros du e to c on s-W
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1965. ec respiratory ap ne d 2: 13Z5'B paratus, ,\110 J. R E1 N AU , {' )I 1A ~S '~ J. A., PITbEllCS'pot ' ~h.l.· SA NP oa D, J. P. : e . ential ro le . 1 pult1 lIY nosocomllJ. tion ~erapy 1965. eq u/ iP ctt na ry m
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fe 4<\-:831'of life! In ~ 10 ROGERs, Dct lo n, . E.: The. 1 di ging pa tt er nEngl. '. th re at en in g. m se as e NeW Mild., 1:677,ic ro bl a ' Cg ,\l lG , 19 59 11 W El N ST26 . )1 El N , L., G OLl;>FlELD 1 /l.Nl' therll:{>1 T .:
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iet!:1S- a study ofnstho~currlng du n posing factors, eir fre~ue~cYj Mild.,and 5 \' 2~7, 2' New ng . . . 1954. lts oll , 12 Ll:l"P£ll, M NO }l F. , }/l.°p/l.'\'15' ., DoEwLS G. G., U C.KH J. c.. ProlonTgeP,d ad"~m. ,OB~Ldo·Sn .ofANant> tibiAot ~ nl l' istr:chial dise m pa tie nt s w ith as e, ch g0 ro 8. nl c ~h mo.#ler microbial Age aj)1, p. nts 4nd e 19
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EOG STUDY IN
PATIENTS W 'l'be authot IT H CONGEN ITAL CARDIA clinical llt at e ll compare4. changes in th C FA IL U R E cardiac faUur of patients suffering frome ECG and ln ve nt rtc le , h e an co w d Ith xeml8. nl re en du l'U lta et lm l lo subclllvlan-pulm onat'Y lnsumci n of Ypo The autbotll f e"eesslV~~ ttl lb \ 0 on en to at' cy un Y d af an no iOg~ te as r va ri an ts -c en tr tomosl.s perfor si s 0 elee the he ar t. eI med In two troelU'" iSOpll ther cllntcalgn tery witb th e al end 0( the severed su tc lY al Jl of ly or in d the 53 pa tie lavian arnt s observeui1 A. cosnpal' stottle-&ubcl.a.vian arpulmonary ar te ry and the bc the two vari an 0 ne te ts w l'Y 0M of m w et a1 tY su ith ho l~ d the l'Ulmonary S\S reveal out th ei r se teelled a dIstinctbclavlan-p .on by means artet'Y wltb· advantage 0 t the ne 'I'bere wall actlpa ot a Wide ho nlQ.U8 of anas ta m lle og to U m ra sn between th osis. ft. ot the: anastom e od f1metl.on di~rapbiC may be as so osis and alterations on thgo Oo NI l"f SK Y. e ei O. EO at A. ed G ' Elett fOC a'. O w AND IVANOV witb th bicn tormed by the A, t, study of patie f" ~ .. ni ta! be ar t muse1e. e Increased. work pernt ,,, rebaC avii\ l'l" partl.cularly by witb pulmonuy s suffering fron> t~atio ns the le ft insuffidency af of sU ~9 61. pu lm on ar y an ter OP(;;SS astoll
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1 ADBNOIDS C A U SI N G PU The syndrome L M O N A llY ot eh ronic upper-alrw HYPERTENSI with resulUng ay obstruCUon al ON ve ol ar by poventilaUon an . monale. is de lllS th re e mon veJlle1ll~ d sc rib co r ths la te r reve d gr ea t l1O~pro ed pu in a tbree-year t«intrasted with In pr ale he lle ar t _A artet essure in the -old child and lU '" vsti0ll ri literature. Hyp the othe:r eight eases re gh t si de al of blood ga ~ pl'88 rted In th e these patlents ercapnIa Is the: key to po and resl.duas l valVes. mUd resid~iC ev Surtl el~ rigllt idence 0 ar t sr electroeardlogr ry hypertensin with otherwise unexplainediagnosis In ve nt ap t,bat pu ricular hypertr tmon op hY airway and nxl'l. E st ab H sh m en t of an d pUlmonaSU te ggest rl al st ru ct ur al cb an NJ naUon resulte ygen administration durin ad eq ua te ge Ill J'" s LI presiSt. N J. lvv. A. M.•• TABA 5. AI'I~.. IJlllOp ttlN. &. pulmonlU'Y arted in a ra pi d and strikIng g catheterW1CZ, R. M.~ Hypertrop S.• HANS?d • causio& ::; - .tl $t1 decUne ot ry pressure. A hi ed ~deC:;':t lthough tollow hypertenswo. an tailllCC, J~,f# lg/. d severe conges up studtive I, M Ill., 221~506, 19 67.
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HAROL D
T
H E INCIDE NCE OF PNEUM ONIA CAUSE D
by the common gram-negative bacilli has increased in the last decade.' Members of the Klebs iella, Escherichia, Proteus, Pseudomonas, and Bacteroides genera are the causative agents in approximately 4 per cent of all pneumonias seen in a large hospital today,' Although this changing pattern of pneum onia can be attributed to many factors, several recent studies have emphasized the importance of serious underlying diseas e in predisposing to gramnegative bacillary pneum onia in man.r" Chronic pulmonary disease, diabetes, alcoholism, and malignancy are known to impair the resistance of the host to bacterial invasion. Concurrently, the presence ofsuch diseases in the host may require the administration of several forms of therapy that further increase the risk of infection. Finally, if hospitalization becomes necessary, there will be the added risk of exposing the susceptible host to the nosoc omial flora of gram-negative bacilli. It should not be surprising that most cases of gram-negative bacillary pneumonia are now acquired as terminal infections in the hospital environment. 1.a 04 The purpose of this report is to describe in detail the circumstances under which fatal Pseudomonas aeruginosa pneumonia appea red in an otherwise healthy middle-aged man. CASE REPORT
A 43-year-old, white painter was in good health until May of 1964 when he developed a sore throat, hoarseness, and a cough productive of small amounts of yellow-green sputum, He consulted a private physician who made a diagnosis of acute bronchitis. Intramu scular injections of procaine penicillin-G were administered daily without improvement. After five days, the penicillin was discontinued and a two-week course of *From the Medical Service, Veterans Administration Center.
tetracycline (Achromycin V) was prescribed. A severe stomati tis ensued with difficulty in mastication, dysphagia, and a 20-pound weight loss. First Hospita l Admissi on: He was admitted to a private hospital on July 27, 1964 for evaluation of cough and stomatitis. His occupation as a house painter did not entail unusual exposure to noxious fumes or sprays. There was no history of vomitin g or excessive alcoholic intake, The results of physical examination were normal, except for diffuse inflammation and dryness of the oral mucous membranes. Candida albicans was isolated from a culture of the tongue. Sputum cultures (3x) yielded Candida albicans and Pseudo monas aeruginosa (few colonies to a heavy growth ), A chest roentgenogram was normal. The only medicat ion the patient received was a nystatin (Mycostatin) suspension administered four times daily, to be held in his mouth and swallowed. Although the patient's cough persisted, the stomati tis improved and he was discharged after ten days of hospitalization, Second Hospita l Admission: He was adminc d to a second private hospital on August 17, 1964because of shortness of breath and wheezing of seven days' duration. Physical examination revealed an acutely ill white man who was dyspneic at rest. The temperature was 101°F (38.3°C). Expirat ory wheezes and rhonchi were audible over both lungs. Sputum cultures (7x) yielded mixed flora with a predominance of Pseudomonas aeruginosa (moder ate to heavy growth), The admission chest roentgenogram was normal. During the first three weeks of hospitalization, he had a daily tempera ture of 101°F (38.3°) that failed to respond to 600,000 units of procaine penicillin-G administered intramuscularly every 12 hours. He became afebrile while receiving oral demethyl chlortetracycline (Dedom ycin), 150mg every six hours, and intramuscular colistimethate (Colym ycin), 150 mg every 12 hours. Because of a poor clinical response to antibiotic therapy, bronchodilating drugs, and expectorants, a fivelobe bronchogram was performed on September 4, 1964 and was interpreted as normal. Subsequent courses of oral chloramphenicol (Chloromyce tin), 250 mg every six hours, and oral erythromycin (I1osone), 250 mg every s~x hours, were administered empirically without Improvement in symptoms. During the last four weeks of hospitalization, he received inhalation therapy
643
for the firs t ti sulfate (1 m me in the form of st re l four times da of 50 m g /m l solution ptomycin ) nebulized ily by in te rm Cultures of it te n t positi the ve pressure. for Pseudom sputum were persiste nt on ly positive as ae rugino roentgenogra ms disclose s4. and repeated ches d t linear and p trations of bo atchy infil· th lungs. In spite of wor in the roen sening n o te tgen d improved su ograms of the chest, his dyspnea fficiently to a ll o w disc eight weeks harge af te r of Third Hospi hospitalization. days at hom tal Admission: D u ri n g the n ex t 11 e, he experi en y w s of co ughing, dysp ced increasing parox ne necessitated a, a n d whe re on October admission to the priv ezing th at ate hospital 24 amination w , 1964. T h e results of physical exere unchange d ture of 100° F (3 7 .8 ° C ). except for a te m p er aS p u tu m cult mixed flora ur w aeruginosll (mith a predominance of Psees yielded udomonas o d er at e to he tion to the pr eviously desc avy g ro w th ). In ad d iri chest roentg enogram re bed abnormalities, the ve area of infi ltration in th aled a m o re discrete e lower lobe lung. of the le ft T h e admissi on diagnosis and b il a te was chronic ra bronchitis cance of th l bronchopneumonia. e repeated T h e signifiisolation of Ileruginosll fr Pse om the spu tum was no udomo1l4$ time. T h er ap t clear at th y was initia e ted w it h 3 per cent so ml luti nebulized th on (2.5 m g /m l) of po of a .25 ree times da ly ily by in te rm myxin B tive pressure . For the fi it te n t posirst oral chloram phenicol (C five days, he received hloromycetin ) in a dose JULY
....UGUST
SEPTEMBER
OCT08ER
NOVEMBER
POLY MYXIN 8 ;;1\~~*1! \ .< ••••.••,.m .
SPUTUM+
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PREDNISONE
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urse an d thera.PY·
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s seUdomona aeruginosa
Tn (~••erythrocyte ta ·...laly . nood e was 42 m m ih I' yvcsteTgren) bl C : trolYle SIJI, w Urea nitrog se ru m el ec r~ "alues re DOnna!. 1'{;; a n d s er y th em a. ti4 a{l..:F..)lac1t o: test, a n d the r..LJeluuplnuat01'd a rt h n.. .J\.) bloOd $" g ex test were n atlY e. A fastin Wa r eg ga .. 0 0 sl /1 g PO r u m o -h 86 o s tw bl nd a S\ve:fllUdial ar Wasm~o~ mI.
m g j1 0 0 Olytod Sug tein elelectr o e ValUes Were S er u m p ro . ph al to ct rm C o 9.06 sis reVealed n e p ro te in of ,; l ta 'nI, ~.rtt Per 0 ml, al b u m ' a to gm p e r 100 l~ct' Ith tnod erate elevati rn 3.83a c h globulin 1lI~ ~Oll. J\n.l111muUoelec On of e di losed n o r. horesis sc J<', 11l1ll1un oP tr . ns li bu glO lor llI lilll sle;...: tests s 1 fixation'te.st ;,J b last° ll ty co ' a n d Com ~enta d opl"'ftPOe _ st "l"01ll lO hi ld S, cc I SI S co S ,n . e -m 1lell'.. rc\'eosj,s were n egatlY S s were o"tI m Culture ~ t fOr Ii U P b' ( co nd . tu Slrell A re i. g n lm )u cu se h st dUt ~h, p p U Wa P O s iteriv e ' rns 25 mm of ruIth Sput berclaho.-'. W w s re r tu fo ul e C iv lt at ~l ere n eg d a Pite baCilli . ~Ot1tine s lt u re s yielde a ,re Cult re o f P.relldPUtunm cu Uginosa an d U T 0 ~olll/J(ed 8 with a I'01nO '!S ae e o f Pseudo. ~ nfl.rC4etu 61r?1loSfl• A. b P edOllUnanc examination tis. e elllb IS, 1964 :C~oscoPic ic bronchi~r ron qlt/'; PseUdo US ino ea ed ch ?ltas ael'ttg sa a n d Stapkywcocc l e er w s e~ m ia \va o ch fr on d te br of llSola SlerjShltJgs• 1J d CUltur anadcu lt.u re oO lt u re were es b \ cu J . le Ie ?' , ur i"·,'ltl OUe ar ro w ex a . Wed m in O sh m » d no lYeloi asp'ra tr: lasia n U lla u lt u re of the rp pe hy te ' and c V. w s Sterile. t.:ls etl.tilat: lunction d te ri al bl oo ill allalYsi ry fO rt n ed o ~ e ~ a n d ar 1964- were I, o~;rpre~ds: ers cOmpatibI .c em b erdera te airway m~ ll io h Ct lt Uta ~U faUe .w ht ygen sat. ig ox sl .. al A ri li te In ar ' 01 ~1l fO e~ eX ' )8 1l W dl1fusio O • problem """ -
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PNEUMON
IA
use, pa tc hy revealed diff ct area of m ra og en tg in en st s w it h a di o f the le ft _ Ches~ ro be of both lung ~filtrat1ons filtration in the lower lo in d se ea mcr ce of . e significan lu n g (F ig 2) mission, th as aeruginosa ad f o e m At the ti Pseudomon d. In view te d isolation of the re p ea te tu m was n o t apprecia timicrobial u an sp e th um tr m ec o sp fr d a ro b ered a "sec ious of the prev organism w a s consid at ed in the e ic therapy, th er " an d was n o t im pl , the predly ad e. According o n d ar y in v of his diseas hdrawn, antimicrobials is es en og th it pa s gradually w th e t diagnostic studie nisone was ed fu r nu d ti on an sc d, di el were w it hh ed. T h e prednisone was g day, the in m were perfor 4-, 1964. On the follow is temperaH er b r. em ve fe ec D of on a recurrence F (38.3C) an d 1030F p a ti en t h a d tw e e n 101° ainder of hospitalizae b ture was rem mplained of il y lor the (3 9 .4 ·C ) da e onset of fever, h e co a an d reth n ng d y sp e tion. With ess, increasi g at the bedside. A kn ea w ed sittin m a rk ac ti vi ty to mg adminis yxin B, 25 was started st ri ct ed his m ly po of se s, five-day cour cularly every six hour effect on his us te re d intram 18, 1964 and h ad no nsidered a co er on Decemb . A lt ho ug h h e was sy was perse op clinical cour risk, an open lu n g bi December p o o r surgical r general anesthesia on basilar segr formed unde superior and posterio m an d rubhe fir T e . er 64 w 19 be , 8 lo 2 easuring up e le ft lower ments of th tency. Small nodules m throughout is ed ns bery in co diameter were pa lp at ic secin . Microscop to 1 em the left lung from the medial f o er d n ai tained the rem discl~ ge biopsy ob tions of a wed t of the le h upp~r I ?h sllpe~lm It en W gm s n Jingular se specific, pneumcm suppuratIon: n. chronic, no flammation and focal d Gomorl in an posed acute a d d ·S ch iR , ultures for , periodic C en s. ls ee sm ni -N ga hI Zie no microor ruses were. negative. ed al ve re stains and vi was r~gmDsa ast bacilli, fungi, acid-f th of Pseudomonas Qe bIOpSy specow from the A heavy gr p u re culture recovered in biopsy. to the lung n tio imen. ac re e vers December He h ad no aderapy was restarted on e, 25 mg ut th ro B P ol ym yx in tramuscular 1 ml o f a th by the in , 30, 1964, bo s, and by inhalation times da!1y ur every six ho g jm l) nebulized four was mamm e 0 (1 pressure. H solution etent positive ereafter with no appr it rm te in by th ic ph en ra m gi og tgen is re tained on th on the clinical or roen 65, h e had 19 , ct ciable effe iJJness. On Ja n u ar y 13 a n ? died course of his t of massive hem?pt-rm (FIg 1). n se io n at o It an ab ru p t rous efforts at resuSC abnor· e th revealed sy despite vigo op cr ne sy at y stem. Examination m it ed to the respirator partially li h it be was filled w was dif. malities to e ronchial tree The tracheob and the mucosal surfacere free of w d oo es bl ac d sp te l ra clot ed. The pleu cut surfaces fusely inflam s were firm and the e a t te re d ng lu ma. S fluid. T h e red parenchy ere many small his ay gr a disclosed hyma w the p a re n c throughout
j j j
j
HAROL D D. ROSE
areas of induration of yellowish discoloration. In the right lower lobe there was a large area of necrosis and cavitation that measured 6 x 10 em in diameter and contained clotted blood. In the left lower lobe there was a similar cavity that measured 3 x 3 cm in diameter. This cavity communicated with a bronchus and had eroded into a pulmonary vein. Frank pus was not encountered in either lung. Microscopic sections of the lungs revealed occasional areas of fibrosis and infiltration with lymphocytes that had replaced the normal alveolar pattern. More striking, however, were areas of severe necrosis occupied by innumerable poly. morphonuclear leukocytes. The walls of the small bronchi and blood vessels that lay adjacent to these microabscesses were infiltrated with acute inflammatory cells. Several small arteries were occluded by a thrombus. In other areas, the alveolar septae were intact and red blood cells were present within the alveoli. The results of special tissue stains and cultures were again negative. A routine culture of both lungs yielded PseudomOll6s aeruginosa in pure culture; 0.5 ml of a ~4.hour old subculture of the organism was in[ected subcutaneously into the abdominal waH of a guinea pig and produced a 3 em in diameter ulceration after 72 hours.
the ~ocal mecha nisms by which the lo",e( respiratory tract clears itself f b ,.;s,. ' H ow~ver, It would appear that 0theiraete.· majot role . IS to alter the systemic d ef ense meo_I.,' arusrns of the host and allow th ftY negativ e bacilli to implan t in es ' pu legt1Lar mon l t Issue.
The common gram-negative bacilli have a low degree of pathogenicity for human pulmonary tissue. If these organisms are to cause pneumonia, they must be able to enter the lower respiratory tract in sufficient numbers, and have their tissue invasiveness enhanced by factors in the host that impair resistance to infection. Forem ost among these many factors is the presence of serious underlying disease in the host. In 1960 ~n.eeland and Pri~e3 reported an increasin~ incidence of terminal gram-negative bacillary pneumonia occurring in patients with such diseases as malignancy hepatic failure ' , u~mla, apoplexy, and conge stive heart failure. Lepper' noted a similar trend in patients who developed pneumonia in a general hospit al from Januar y 1960 to March 1962. More recently Tillotson and L emer1 reporte ' d their experie nces with 38 cases of gram-negative bacillary pneumonia ~een at the Detroit Receiving Hospital dur109 a 12-month period. Thirty-six of their cases h~d serious chronic diseases including alcoholism, congestive heart failure, diabetes, and chronic lung disease. The presence of such diseases in the host may suppress
.
Many ~ronically ill patients will eve~' tu~lly req~lre a form of therapy for th el! prImar y dlSo~der ~hat is known to further ~ncre~se. the risk of mfection. Corticosteroi~' Irradiation, and cance r chemothe apelltlC drugs may be indicat ed in the man:geJJ1eflt of these patient s and are capable of sur pressing the inflam matory or leukoc ytic response of the host. Proble ms in venule.' tion may arise and necessitate the use of prolonged trache al intuba tion or tracheostomy. The presence of an airway in tit' trachea will not only create a direct co~ munica tion with the enviro nment but ",iU act as a foreign body and facilit ate tlI' colonization of gram-n egative bacilli in tll~ mucosa of the lower respiratory passages, Finally, several recent investi~tions bave defined the hazard associated with the 1l~ of contam inated mecha nical respiratOrsReinar z et al have demo nstrat ed verY clearly that the gram-n egative bacilli are the major contam inants of inhalat ion ther~ apy equipm ent. In contra st to the other common pathogens, t h es e organisms can survive and multiply in a humid environ' ment, If the inhalat ion therap y equipment is not properly decont aminat ed, large nllnl~ bers of gram-n egative bacilli can be aero~ solyzed and carried into the lower respiratory tract of susceptible patients..\lthOllgh these modes of therap y constitute important, advanc ements in the care of the chronicalh ill patient, there is no quesiton that the risk of infection is increased when these agents are administered either alone or in com~ bination, Certainly, the hazar d of cro:s~ infection from the nosoc omial bactenal flora must be kept in mind when such treat· ment is undert aken in the hospital enviro n'
ment, In the patient presented here, the onset of the fatal Pseudo monas pneum onia could
Volume 53. No. 5 May, 1968
CHRONIC
Pseudomonas aeruginosa
not be attributed to any of the above-mentioned factors. A careful clinical and necropsy study failed to disclose the presence of an underlying disease. Although the patient did receive inhalation therapy and corticosteroids, they were both administered after the pulmonary infection was well established. Furthermore, the circumstances under which the illness developed and the isolation of the causative agent from the initial sputum culture are evidence against the infection being hospital acquired. It would appear that the onset of the Pseudomonas pneumonia could be attributed to a single major factor, namely, the administration of "broad spectrum" antibiotics with the subsequent alteration in the bacterial flora of the respiratory tract. The replacement of the susceptible bacterial flora by resistant "opportunistic pathogens" is one of the well-recognized ecologic changes caused by antibiotic therapy. Rogers" and others have emphasized the importance of this selective action of antibiotics in the overall increase in the number of gramnegative bacillary infections seen today. In a postmortem bacteriologic study of pneumonia, Kneeland and Price" also concluded that the introduction of antibiotic therapy ?as played a major role in the increasing Incidence of gram-negative bacillary pneumonia. It should be emphasized again that this study concerned a population of serioU'>1y ill patient'! in whom the antibiotic therapy was but one of several factors that may have predisposed to this type of infection. In contrast, the use of antibiotics in the treatment of ambulatory patients with mild respiratory infections provides an opportunity to evaluate the role of these agents alone in predisposing to gram-negative bacillary pneumonia. As might be anticipated, Weinstein and associates" found Only three cases of pneumonia of all types Complicating the antibiotic treatment of approximately 1,500 patients with otitis media, pharyngitis, or tracheobronchitis. One case each was caused by Pseudomonas aeruginosa, Hemophilus inlluenzae, and an Unknown gram-nep;ative organism. Lep-
PNEUMONIA
per':" studied the same problem in a group of
1
1
HAROLD D. ROSE
very rare. Nev ertheless, the ou tcom present patient demonstrates th e ~n th e occur and indi cates th at earl a~ ~bis can y cllIDCal and bacteriologic re cognition of th e tion is mandato ry if proper tr super~fec eatment IS to be instituted, Rl
!.I1E1l.l!.NCES 1 PIEII.CE, A. K. ., ED M ON SO N, E. K.l!.
'tCltl!.IlSID,
J., Lo
B., MCGEE, G .,
UD O N, R. J. P.: An G. AN SA t!l 'O 'R D, gram-negativanealys1S of factors. predI!tspo ba ci lla ry necrotizing pn slng .to Amer. Rell. Re 2 TI LL OT SO N, s;. Dis., 94-:309, 1966eumonia, J. R. AND LEIlNE'lt, . monias caused by gram-nega. A. M.~ Pn eu i, in , (Balt.), 45 tive baciUi, M ,d · :65, 1966. 3 K. Nl !.E l.A ND , Y • biotics and te ., JR. AND Pa lO l!. , K. .M microbiologicalrmmal pneumonia - post.: Antlm study, A m ". tem 1960. l- Mild., 29or :967, 4 L E ns ». , M. H . rod pulmonar .: Opportunistic gram y infections, atIVe Dis. Ch,n,-neg 1963. 44 : 18, 5 TUWEVALL, G .: Bacteriolo nursing of tra gi ca l as pe ct S,o.nd., 31 cheotomi'Zed patients, s on the 6 ME"P.TZ, J.6J.(Suppl. 154) :91, 1956.Acta M ,d. SC ltA U ll, L. J. R.: A hosp, ita AND MCOLl! .MENT~ l outbreak of Klebsiella pn eu -
in~tion .t';:~~: ·w eontaJ;1lin at ed aeroso k;~ RssP, DIs., l solutions,
moniae from
95 :4 54 , 1967 .
S ,..
ltU-L M. C., 7 McNA1It....1lA B....L~~t~tio. , M. 1. . A ~udy ...NO Tu cl tE B th e Ann. In" ll. , E; bo " ·tal infecto.f . e pa tte rn s ions, OL l ed 66 :4 80 , 1967Sp tJl la& . G 8 PHU"-t:lPS, 1. ' ps eu do . Ol S NOEll. ,,·ed .• • AN D tl1 Pt i.o n11 .1l n ..• ae ru gm os a cros du e to c on s-W
~
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1965. ec respiratory ap ne d 2: 13Z5'B paratus, ,\110 J. R E1 N AU , {' )I 1A ~S '~ J. A., PITbEllCS'pot ' ~h.l.· SA NP oa D, J. P. : e . ential ro le . 1 pult1 lIY nosocomllJ. tion ~erapy 1965. eq u/ iP ctt na ry m
LA
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fe 4<\-:831'of life! In ~ 10 ROGERs, Dct lo n, . E.: The. 1 di ging pa tt er nEngl. '. th re at en in g. m se as e NeW Mild., 1:677,ic ro bl a ' Cg ,\l lG , 19 59 11 W El N ST26 . )1 El N , L., G OLl;>FlELD 1 /l.Nl' therll:{>1 T .:
Jpe,
"n • ch emo
In fe ct io
iet!:1S- a study ofnstho~currlng du n posing factors, eir fre~ue~cYj Mild.,and 5 \' 2~7, 2' New ng . . . 1954. lts oll , 12 Ll:l"P£ll, M NO }l F. , }/l.°p/l.'\'15' ., DoEwLS G. G., U C.KH J. c.. ProlonTgeP,d ad"~m. ,OB~Ldo·Sn .ofANant> tibiAot ~ nl l' istr:chial dise m pa tie nt s w ith as e, ch g0 ro 8. nl c ~h mo.#ler microbial Age aj)1, p. nts 4nd e 19
61.
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V /. llo sp lta Fo r re pn.nt s, , ~ase wn'te.• Dr Rose, Wood, WiscoPl . nsm.
EOG STUDY IN
PATIENTS W 'l'be authot IT H CONGEN ITAL CARDIA clinical llt at e ll compare4. changes in th C FA IL U R E cardiac faUur of patients suffering frome ECG and ln ve nt rtc le , h e an co w d Ith xeml8. nl re en du l'U lta et lm l lo subclllvlan-pulm onat'Y lnsumci n of Ypo The autbotll f e"eesslV~~ ttl lb \ 0 on en to at' cy un Y d af an no iOg~ te as r va ri an ts -c en tr tomosl.s perfor si s 0 elee the he ar t. eI med In two troelU'" iSOpll ther cllntcalgn tery witb th e al end 0( the severed su tc lY al Jl of ly or in d the 53 pa tie lavian arnt s observeui1 A. cosnpal' stottle-&ubcl.a.vian arpulmonary ar te ry and the bc the two vari an 0 ne te ts w l'Y 0M of m w et a1 tY su ith ho l~ d the l'Ulmonary S\S reveal out th ei r se teelled a dIstinctbclavlan-p .on by means artet'Y wltb· advantage 0 t the ne 'I'bere wall actlpa ot a Wide ho nlQ.U8 of anas ta m lle og to U m ra sn between th osis. ft. ot the: anastom e od f1metl.on di~rapbiC may be as so osis and alterations on thgo Oo NI l"f SK Y. e ei O. EO at A. ed G ' Elett fOC a'. O w AND IVANOV witb th bicn tormed by the A, t, study of patie f" ~ .. ni ta! be ar t muse1e. e Increased. work pernt ,,, rebaC avii\ l'l" partl.cularly by witb pulmonuy s suffering fron> t~atio ns the le ft insuffidency af of sU ~9 61. pu lm on ar y an ter OP(;;SS astoll
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1 ADBNOIDS C A U SI N G PU The syndrome L M O N A llY ot eh ronic upper-alrw HYPERTENSI with resulUng ay obstruCUon al ON ve ol ar by poventilaUon an . monale. is de lllS th re e mon veJlle1ll~ d sc rib co r ths la te r reve d gr ea t l1O~pro ed pu in a tbree-year t«intrasted with In pr ale he lle ar t _A artet essure in the -old child and lU '" vsti0ll ri literature. Hyp the othe:r eight eases re gh t si de al of blood ga ~ pl'88 rted In th e these patlents ercapnIa Is the: key to po and resl.duas l valVes. mUd resid~iC ev Surtl el~ rigllt idence 0 ar t sr electroeardlogr ry hypertensin with otherwise unexplainediagnosis In ve nt ap t,bat pu ricular hypertr tmon op hY airway and nxl'l. E st ab H sh m en t of an d pUlmonaSU te ggest rl al st ru ct ur al cb an NJ naUon resulte ygen administration durin ad eq ua te ge Ill J'" s LI presiSt. N J. lvv. A. M.•• TABA 5. AI'I~.. IJlllOp ttlN. &. pulmonlU'Y arted in a ra pi d and strikIng g catheterW1CZ, R. M.~ Hypertrop S.• HANS?d • causio& ::; - .tl $t1 decUne ot ry pressure. A hi ed ~deC:;':t lthough tollow hypertenswo. an tailllCC, J~,f# lg/. d severe conges up studtive I, M Ill., 221~506, 19 67.
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