Klebsiella Pneumonia

Klebsiella Pneumonia A Review of Forty-five Cases and Re-evaluation of the Incidence and Antibiotic Sensitivities*

T . LAMPE, II, M.D.** York, Pennsylvania

WILLIAM

K

INCIDENCE

L EBS IE LLA PNEUMONIAE WAS DISCOV-

ered in 1882 by Friedlander. He believed that this organism was the sole cause of pneumonia. This idea was corrected a few years later when other workers showed that the Diplococcus pneumoniae was the causative organism in most cases of pneumonia. Several good reviews of Klebsiella pneumoniae were published prior to the advent of the antibiotic era .': Table 1 summarizes the mortality from Klebsiella pneumoniae in papers containing significant numbers of patients reported since 1937. Recently, the course of the disease has been changed due to the use of streptomycin and chloramphenicol.' MORTALITY

TABLE I FOR KLEBSIELLA

Burrows' points out that pneumonia due to Klebsiella made up 0.5 to 4.0 per cent of aU pneumonias. Pearlman and Bullowa' found that 0.5 to 2.0 per cent of all pneumonias were due to Klebsiella. Most cases of bacterial pneumonia today are successfully treated in the home or clinic with penicillin and other antibiotics producing dramatic results. It is usually only the complicated cases or those responding poorly that are referred to the hospital. It is from the latter group that the incidence of Klebsiella pneumoniae is usually calculated which probably gives a slightly higher than actual incidence. Hines Hospital cases of pneumonia are admitted to the wards for treatment since no outpatient facilities exist. From January, 1948 to January, 1958, there were 7, 117 cases of pneumonia of all types diagnosed and treated at the Hines Hospital. This number includes new admissions and patients who developed pneumonia in the hospital. Forty-five of these cases were diagnosed as Friedlander's pneumonia, an incidence of 0.65 per cent. This low incidence is probably a better estimate of the actual incidence than previous estimate'> would indicate. All the patients in this series were adult men.

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CRITERIA FOR DIAGNOSIS AND METHODS

The purpose of this article is to reevaluate the incidence of Friedlander's pneumonia, to emphasize the increase in complications and survival, and to assess the in vitro sensitivities of Klebsiella pneumoniae to the antibiotics in current use.

The basis for diagnosis in this series was the isolation of Klebsiella as the sole or predominant organism in one or more cultures obtained from sputum, bronchial washings, purulent bronchial drainage, or from the lung parenchyma at necropsy. Patients were selected for inclusion in this group by three methods. They were encountered clinically on the wards or they

·From the Department of Internal Medicine, York Hospital. ··Study and data collected while a Resident on the Medical Service, Veterans Administration Hospital, Hines , Illinois.

599

Diseases of the Chest

WILLIAM T. LAMPE, IT

600

were cross-indexed as Klebsiella infections in the record room. A few additional cases were uncovered by a survey of all of the sputum cultures done between 1948 and 1958 where there was a clinically significant pneumonic infection. The question naturally arises, is the isolation of Klebsiella in the sputum diagnostic of an infection with this organism? It seems reasonable to believe that where there is a clinical pneumonia and Klebsiella is isolated in the sputum as the sole or predominating organism that this organism is etiologic. Klebsiella is not part of normal flora for the upper respiratory tract, sinuses, or mouth although carriers have been reported . The selection of cases reviewed here are based on this assumption which is open to criticism until better methods are made available. CLASSIFICATION

Several classifications have been proposed. Erasmus' in 1956 designed a classification which he recognized as artificial. He divides Klebsiella infections into primary, acute and chronic, and secondary which are associated with other organisms. Chronic primary infections, as defined by Erasmus, are those lesions which last six weeks or longer. Ritvo' proposed a roentgen classification which is useful, but made no room for the evolution of the disease process: 1. Massive lobar consolidation type (bulging of affected lobe) . 2. Lobular consolidation characterized by patchy irregular densities early, which later develop into confluent consolidation. 3. Chronic form characterized by lung abscess or cavity. Here also there is some overlap since patients with massive consolidation often develop abscess and cavitation and, therefore, must be included in both groups 1 and 3 above. Probably the most workable classification is that proposed by Gill.' 1. Acute Friedlander's pneumonia a. Sputum pure or predominantly Klebsiella.

b. Acute pneumonia. 2. Acute mixed infection or secondary Friedlander's pneumonia. a. Mixed pathogens when first seen. b. Klebsiella pneumoniae superimposed on a prior pneumococcal pneumonia. c. Came to hospital with long standing untreated pneumonia. Sputum showing predominantly Klebsiella. 3. Chronic Friedlander's pneumonia a. Several months duration when first seen and sputa contained mixtures of organisms. The classification proposed by Gill is probably best from the clinical and bacteriologic point of view. More and more of the patients treated with broad spectrum antibiotics are surviving the acute primary stage to acquire mixed infections of a chronic nature. Using Gill's classification of acute, acute mixed, and chronic, 20 of the 45 cases in this series were acute, 15 were acute mixed, and 10 were chronic. Graph 1 relates the age distribution to the deaths in this series. The incidence of deaths increased with age. Eighty per cent of the deaths were in patients over 50. Most of the infections occurred in the 50 to 60 age group. The higher death rate at 60 or older is probably due to decreased resistance to infection and co-existence of other disease. PRESENT SERIES

The present cases numbered 45. The average age was 50. Ten of the 45 paTABLE 2-RESULTS OF ANTIMICROBlAL THERAPY Drug Cases Penicillin 9 Penicillin and sulfa drugs 2 Penicillin and streptomycin 7 Penicillin, streptomycin and broad spectrum antibiotics 13 Penicillin and broad spectrum antibiotics 10 Broad spectrum antibiotics 3 Penicillin , streptomycin and ACTH 1 Total 45

Complication Deaths 0 1 2 3

2

4 1

2 0

0 10

1 9

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KLEBSIELLA PNEUMONIA

tients died and necropsies were performed on five. Cultures of the lungs at necropsy showed pure growth of Klebsiella in three of the five. Sixteen of the group were known to be severe chronic alcoholics and several others admitted to moderate drinking. Twenty-three patients had pure cultures of Klebsiella in the sputum, tracheobronchial secretions, or lung tissue, the latter being obtained at necropsy. The mortality and the results of therapy are indicated in Table 1 and Table 2. Forty-four of the 45 patients were treated with antibiotics. One who received no treatment had spontaneous resolution of mild bronchopneumonia. Forty-two received penicillin alone or in combination with other antibiotic agents. Nine received penicillin alone and only one of these died. All treated with penicillin alone had mixed infections. Table 3 shows that 11 developed complications; four of these came to surgery for drainage or resection of a cavity or empyema. TABLE 3 SURGICAL PROCEDURES AND COMPLICATIONS

,

Complication Empyema Pleural effusion Cavitation Total

Number of Cases 3

5 3 II

Surgery 3 0 1 4

BACTERIOLOGY

Klebsiella pneumoniae was described by Friedlander to be a non-motile, non-spore forming, encapsulated, gram-negative rod which' produces a mucoid, slimy growth. Many authors have advocated reclassification of the coliform bacteria, most recently Weiss et ai.· in an excellent review article. In Bergey's M anuaf the Klebsiella is grouped under the Escherichiae as follows: Escherichiae : a. Bact. coli b. Bact. aerogenes c. Klebsiella pneumoniae Edwards" also points out that there is no satisfactory method of distinguishing between Klebsiella and Aerobacter at present

601

and they should be considered a single group. A reclassification seems to be in order at this time for several reasons. First, Klebsiella and Aerogenes are difficult and in many instances impossible to differentiate culturally. Second, such a differentiation serves no good purpose from the point of view of therapy since both organisms cause similar infections which require similar therapy. Both species should be included together under one name. The patients included in this series all had organisms which were considered to have more of the cultural characteristics of Klebsiella than of Aerobacter. ROENTGEN FEATURES

The roentgen features have been ably reviewed by Holmes.II When present, the following should suggest the diagnosis of Friedlander's pneumonia : 1. Bulging fissures. 2. Sharp margins of the advancing border of the pneumonic infiltrate. 3. Early abscess formation. It is well known that the upper lobes are by far the most common site of involvement. This was true of this series. Failure of resolution in the time expected for pneumonia to improve or resolve should raise the question of Friedlander's pneumonia in the differential diagnosis. It is easy to see how Friedlander's pneumonia could be mistaken for tuberculosis since the roentgen appearance may be similar. There are other features which serve to confuse the clinician . Both these diseases occur most commonly in the upper lobes and can produce cavities with pleural thickening, fibrosis, and similar type of contraction and distortion of the fissures. For this reason, it may be wise to withhold streptomycin in a few selected cases which do not have an overwhelming infection and to obtain three smears and cultures for Mycobacterium tuberculosis while treating energetically with tetracyclines and chloramphenicol. Four of the patients in this series of 45 had tuberculosis. Two of the four had previously known inactive

WILLIAM T. LAMPE, n

602

tuberculosis at the time they contracted Friedlander's pneumonia and two had active tuberculosis with Klebsiella superinfection. In some other cases, there was strongly positive skin reactions to purified protein derivative (PPD), so that this was no aid in ruling out tuberculosis. A negative PPD test would have been of great value in these cases and therefore should always be performed . PATHOGENESIS It is well established that a small number of people are carriers of Klebsiella in the upper respiratory tract. This carrier state has been variously estimated from 2 to 25 per cent as mentioned by Cecil.II Also, a number of authors as cited by Erasmus' in his series of 17 cases states that all of the patients except two showed clear-cut evidence of upper respiratory tract infection such as dental and gingival sepsis, recurrent tonsillitis, chronic otitis media, and chronic sinusitis. In cases where a careful search is made such upper respiratory foci of chronic infection will be found. These foci of infection make excellent sites of origin for aspiration and subsequent pulmonary infection. Since most Klebsiella infections are in the right upper lobe or the posterior portion of the apical segment of the right lower lobe, the evidence seems to point to aspiration as the mode of infection. CLINICAL FEATURES The patients in this series were not unusual from the clinical point of view. The disease pattern has been well described by many authors. The onset is usually acute , often in a chronic alcoholic with high fever, pleuritic pain, and typical sputum which is bloody, sticky and viscous. Gram stain

Diseases of the Chest

of the sputum mayor may not show gram negative, encapsulated bacilli. The upper lobes are the most common sites of involvement . Smears, cultures, and tuberculin skin testing, should always be performed. ANALYSIS

OF

From March 10, 1954 to April 23, 1958, an estimated 6,000 sputa and bronchial washings were examined in the bacteriology laboratory at Hines Hospital (Table 4). Sputa were cultured on blood agar over 24 to 48 hours and then subcultured for isolation and sensitivity testing by the plate dilution method. Sensitivities against the following antibiotics were performed: penicillin, streptomycin, tetracycline, chloramphenicol, erythromycin . A few of the Klebsiella were tested against chlortetracycline and oxytetracycline, but the numbers were so small they were dropped from the series. Of the 6,000 sputa, 397 contained Klebsiella, 68 of these 397 cultures showed a pure growth of Klebsiella, 128 were cultures where Klebsiella was mixed with one other organism, 201 were cultures where Klebsiella was mixed with two or more organisms. Of the 397 sputa where Klebsiella was isolated, sensitivity tests were done in only 161 instances or roughly 49 per cent. All sensitivities were done by the plate dilution method. The results of the sensitivities are tabulated in Table 5. It should be noted that the sensitivities are tests done in glass on artificial media and that these are only indications of potential effects of these agents in body fluids. The sensitivities are valuable to indicate the probable best antibiotic, but must be performed serially if TABLE 5-ANTIBIOTIC SENSITlvmES OF KLEBSIELLA IN VITRO BY PLATE DILUTION METHOD IN 161 ISOLATED STRAINS

TABLE 4-AN"LYSIS OF 6,000 SPUTA FROM M"RCH 10, 1954 TO APRIL 23, 1958 Sputa Number containing Klebsiella Pure culture of Klebsiella Klebsiella plus one other organism Klebsiella plus two other organisms Sensitivities determined on Klebsiella

6000 397 68 128 201 161

IN VITRO SENSITlVlTIES

Drug Penicillin Streptomycin Tetracycline Chloramphenicol Erythromycin

Concentration of antibiotic in units or micrograms/ml Non5 10 Sensitive 1 0 4 5 152 97 16 7 41 90 3 35 33 36 74 35 16 28 38 90 5

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KLEBSIELLA PNEUMONIA

the development of antibiotic resistance is to be discovered. Reports of Klebsiella resistance to streptomycin'" have been frequent since 1947 and more recently, in 1950, the development of chloramphenicolresistant and chloramphenicol - dependent variants of Klebsiella in vitro was reported." THERAPY

Weiss and associates" state that in vitro studies suggest 93 per cent of Klebsiella strains are sensitive to streptomycin or chloramphenicol or both of these agents. Jervey" concluded in 1957 from an experience of 30 cases that every case should be treated with a combination of tetracycline, streptomycin, and sulfonamide. More recently streptomycin has been recommended in doses of 2 to 4 grams daily along with 4 grams of tetracycline for several weeks.l' Streptomycin and chloramphenicol appear to be the drugs of choice, but in some instances tetracycline may be of value. The sensitivities determined in this study (Table 5) support this statement. Streptomycin is probably the most effective agent and should be given in doses of one to two grams intramuscularly each day during the acute phase of the infection. Table 5 indicates that chloramphenicol

should be nearly equally effective in most instances if the blood concentrations reach 5 to 10 microgramsyrnl. By administering 2 to 4 grams of chloramphenicol daily concentrations of 5 to 10 micrograms can be achieved and, if given early in the disease, therapeutic effect may be expected. Early diagnosis of Klebsiella infection and early treatment with adequate doses of streptomycin and chloramphenicol will reduce complications . Drug resistance may develop and then a change of antibiotic may be necessary during therapy. It is well, for this reason, to repeat the in vitro sensitivities several times during the course of any Klebsiella infection. Is the use of penicillin justified in mixed infections in which Klebsiella is one of the offending organisms? Four of 161 strains were sensitive to penicillin concentrations of 5 units per ml., a level which could easily be achieved in the body fluids. The antibiotics used are generally effective, but other factors may contribute to a poor response to treatment. These are: 1. Tendency in this economic group to delay admission preventing early diagnosis and treatment. 2. Patients who die are most frequently alcoholics.

AOE DISTIUBUTION OF KLEBSIELLA INFECTION AND DEATHS

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WILLIAM T. LAMPE, II

3. Lowered host resistance. 4. Presence of bacteremia and leukopenia are of serious prognostic significance. Postural drainage by the elevation of the foot of the bed and the use of the knee-chest position is often of great value where there is an abscess. Bronchodilators by the systemic or aerosol route may also be of value in facilitating drainage. Bronchoscopy may induce profuse drainage of purulent material by dilation of the orifice of the affected lobe with epinephrine on a small pledget of cotton through the bronchoscope. THE USE OF ACTH

AND

STEROIDS

The lowered host resistance and debilitated condition of most patients on admission who have acute Friedlander's pneumonia is well known . The moribund condition of many patients brings up the question of the use of steroids as a life-saving measure. Most of the patients in this series, and in most other reported series of acute Klebsiella pneumonia who died did so within the first 24 hours after admission. It is in this group that steroids might be lifesaving. Intravenous ACTH was used along with penicillin and streptomycin in one case in this series for eight hours, but the patient expired. Jawetz et al." point out that in a large variety of experimental infections it is established that cortisone and other steroids promote the spread of the infecting agent and impair the normal host defenses,":" but in some infections due to gram negative organisms steroids are useful and beneficial." J awetz and colleagues found that cortisone had a significant beneficial effect on the survival of mice weighing 24 to 26 grams and infected with Klebsiella pneumoniae when protected with chloramphenicol. The dose of cortisone was I mg/kg./ day which was beneficial. Larger doses of cortisone or the same doses in smaller animals gave deleterious effects, These experiments in mice suggest that small doses of hydrocortisone, 50 to 100 mg. every 12 hours may be beneficial in man in acute

Diseases of the Chest

overwhelming Klebsiella infections and deserve further trial. Hydrocortisone is recommended because poor condition of patients initially makes parenteral administration of drugs necessary. DISCUSSION This study serves to point out the increasing survival of patients who develop infections with Klebsiella organisms. This decrease in mortality is due to the impact of antibiotics on the offending pathogens which permits the host defenses better opportunity to cope with the infection. The complications are increasing and will increase further as more patients survive the acute phase of the infection. Energetic and early treatment with streptomycin and chloramphenicol in adequate doses is paramount. A combination of agents is to be recommended since resistant organisms have developed to both streptomycin and chloramphenicol. In vitro testing of Klebsiella organisms to combinations of antibiotics should also be considered in unresponsive cases or where resistance to anti biotics develops. By employing two antibiotics the emergence of resistance to one may be lessened. Serial cultures with sensitivity determinations are the only available methods at present to detect the emergence of resistant Klebsiella and may therefore be of help in modification of the antibiotic regimen during the course of the disease. Fever, leukocytosis, increased cough, and change in the character of the sputum are signs which also indicate that therapy is ineffective and that a change in antibiotics is indicated. All too often these clinical signs are minimal. Roentgen evidence of progression with cavitation and spread of the pneumonitis may be a useful guide. Serial chest x-ray examinations should be performed for this reason. ACTH and steroids should be given in small doses to patients with overwhelming infection whose defense mechanisms are not functioning adequately as evidenced by leukopenia, malnutrition, and debilitation or involvement of more than one lobe of the lung . I would give 50 to 100 mg. of

Volume 46. No.5 November 1964

KLEBSIELLA PNEUMONIA

hydrocortisone intravenously along with chloramphenicol 100 to 200 mg. intravenously every 12 hours for two to three days or until the critical period is over. Small doses of steroids are protective in mice as stated previously. It may be that mortality which is so high in the first 24 to 48 hours after admission can be reduced by the use of steroids. Further work is needed to clarify this point. Klebsiella pneumonia may occur at any age. It can be seen in Graph 1 that most of the infections in this series were found in the 51 to 60 age group and most of the deaths in the 61 to 70 age group. Host resistance would appear to play an important part. In malnourished individuals who have vitamin deficiencies, protein deficits, as well as cirrhosis, a so-called permissive effect may be manifested which may account in part for Klebsiella infections. SUMMARY

The incidence of Klebsiella pneumonia is less than one per cent of all pneumonias. Forty-five Klebsiella pneumonias are reviewed. The mortality was 21 per cent. The results of antimicrobial therapy are analyzed in relation to the in vitro antibiotic sensitivities. These in vitro sensitivities on 161 strains of Klebsiella indicated that streptomycin and chloramphenicol are the drugs of choice. Streptomycin appears greatly superior to chloramphenicol in vitro. Streptomycin should always be used in combination with chloramphenicol. ACKNOWLEDGMENT : I wish to express my appreciation to Armand Littmand, M.D., Chief of Medical Service, Hines Hospital, Hines, Illinois, for his many helpful suggestions and review of this manuscript, also to William Weiss, M.D., of Philadelphia for his many helpful suggestions. RESUMEN La frecuencia de la neurnonia de Klebsiella es menor de I por ciento de todas las neumonias. La mortalidad fue de 21 por ciento . Se analizan los resultados del tratamiento antimicrobiano en relaci6n con la sensibilidad in vitro . Estas sensibilidades in vitro de 161 cepas de Klebsiella indicaron que la estreptomicina y el c1oramfenicol son las drogas de elecci6n . La estreptomicina debe usarse siempre en combinaci6n con el cloramfenicol.

RESUME La frequence de la pneumonie a bacilles de Friedlander n'atteint pas I % de toutes les pneumonies. Quarante-cinq pneumonies a bacilles de Friedlander sont passees en revue. La mortalite a etc de 21 %. Les resultats du traitement antimicrobien sont analyses en fonction de la sensibilite antibiotique in vitro . Ces sensibilites in vitro sur les 161 souches de bacilles de Friedlander montrerent que la streptomycine et Ie chloramphenicol sont les produits de choix. La streptomycine semble etre grandement superieure au chloramphenicol in vitro. La streptomycine devrait toujours etre utilisee en association avec Ie chloramphenicol. ZUSAMMENFASSUNG Die Haufigkeit von Klebsiella-Pneumonie betragt weniger als I % von allen Pneumonien. Es wurden 45 Klebs iella-Pneumonien analysiert. Die Sterblichkeit lag bei 21 %. Die Ergebnisse der antimikrobiellen Therapie wurden verglichen mit der antibiotischen Sensibilitat in vitro . Diese Sensibilitat in vitro der 161 Klebsiella-Starnme ergab, da~ Streptomycin und Chloramphenicol die Mittel der Wahl darstellen. Das Streptomycin scheint in vitro dem Chloramphenicol ganz erheblich iiberlegen zu sein. Das Streptomycin rnujl aber immer in Kombination mit Chloramphenicol zur Anwendung gelangen . REFERENCES SOLOMON, S. : "Primary Friedlander Pneumonia," ].A.M.A., 108:937, 1937. 2 PERLMAN, E. AND BULLOWA, J. G. M.: "Primary Bacillus Friedlander Pneumonia," A.M.A. Arch . Int. Med., 67:907, 1941. 3 jERVEY, L. P.: "Treatment of Acute Friedlander's Bacillus Pneumonia," A .M.A. Arch . Int . Med ., 99 : 1, 1957. 4 BURROWS, W.: Textbook of Microbiology , 17th Ed., W. B. Saunders Co., Philadelphia, 1959. 5 ERASMUS, L. D. : "Friedlander Bacillus Infection of the Lung," Quart. ]. Med., 25 :507, 1956. 6 RITVO, M. AND MARTIN, F.: "Clinical and Roentgen Manifestations of Pneumonia Due to Bacillus Mucosus Capsulatus," Am. ]. Roent., 62 : 211, 1949. 7 GILL, R. J.: "Treatment of Friedlander's Pneumonia," Am, ] , Med. Sci., 221:5,1951. 8 WEISS, W., EISENBERG, G. M., SPIVAK, A., NADEL, J., KAYSER, H. L., SATHAVAaA, S. AND FLIPPIN, H. S. : "Klebsiella in Respiratory Disease," Ann. Int . Med., 45 : 1010, 1956. 9 BERGEY, D. H.: Manual of Determinative Bacteriology, 6th Ed., Williams and Wilkins, Baltimore, 1948. 10 EDWARDS, P. R. : "Relationships of Encapsulated Bacilli with Special Reference to Bact. Aerogenes," ]. Bacteriology, 17: 339, 1929. 11 HOLMES, R. B.: "Friedlander's Pneumonia," Am . ]. Roentgenol. , 75 : 728, 1956.

606

WILLIAM T. LAMPE, II

12 CECIL, R . L. AND LOEB, R. F. : Textbook of Medicine, 10th Ed ., W. B. Saunders, Philadelphia, 1959 . 13 MEADS, M . AND HASLAM, N. M . : "Quantitative Studies on the Origin of StreptomycinFast Variants of Klebsiella Pneurnoniae," j. Immunol., 63: 1, 1949. 14 PAINE, T . F. A:-:D FINLAND, M . : "Streptomycin Sensitive, Dependent, and Resistant Bacteria," Science, 107: 143, 1948 . 15 GOCHE, T . M. AND FINLAND, M . : "Development of Chloramphenicol-Resistant and Chloramphenicol-Dependent Variants of a Strain of Klebsiella Pneumoniae," Proc, Soc. Exp , Bio. and Med., 74 :824, 1950 . 16 Committee Report (Am. Coli. Chest Physicians) : "Chemotherapy of Specific Infectious Diseases of Lower Respiratory Tract," Dis. Chest, 33:435, 1958. 17 JAWETZ, E., MERRILL, E. R. AND CHANDLER, L.: "Limited Beneficial Effect of Cortisone in Experimental Klebsiella Infections of Mice Treated with Chlortetracycline," Antibio. and Chemother., 5 : 643, 1955.

Diseases of the Chest

18 THOMAS, L. : "Infectious Diseases; Effects of Cortisone and ACTH on Infection," Ann. Rev. Med., 3: I, 1952 . 19 MONTGOMERY, M. M., BENEDEK, T . G. AND POSKE, R. M . : "Relation of ACTH and Cortisone to Infection," Med. Clin . N. Amer. , 39 : 81, 1955 . 20 ROBINSON, H . J ., MASON, R. C . AND SMITH, A. L . : "Beneficial Effects of Cortisone on Survival of Rats Infected with D . Pneumoniae," Proc, Soc. Exp. Bio. and Med ., 84 : 312, 1953 . 21 HYDE, L . AND HYDE, B. : "Primary Friedlander Pneumonia," Am. I. M ed . s«, 205: 660, 1943. 22 WYLIE, R. H . AND KIRSCHNER, P. A. : "FriedHinder's Pneumonia," Am . Rev . T'uberc., 61: 465 , 1950 . 23 LIMSON, B. M., ROMANSKY, M. J . AND SHEA, J. G.: "Evaluation of Twenty-Two Patients with Acute and Chronic Pulmonary Infection with Friedlander's Bacillus," Ann . Int. M ed., 44: 1070, 1956 . For reprints, please write Dr. Lampe, 436 West Market Street, York, Pennsylvania.

MULTIPLE BILATERAL PULMONARY ASPERGILLOMATA A woman. aged 62. suffered from bilateral multiple pulmonary asperglllomata and progressive polyarthrItis and syphilis. For both the latter diseases she had been treated for a long time with cortisone and penIcillin . The diagnosis of aspergillosis was based on the repeated finding of aspergl11l In the sputum both by microscopy and on culture. together wIth a charaftterlstlc radiographic picture. The strain of

fungi was Identified as AspergillMs Itrr~MS Thorn. The stimulating Influence of cortisone and penIcillin on the subsequent development of a mycotic disease In a subject with a decreased resistance to Infectlon Is emphasized. Z., VIKUCKY . ]. "NO TO....NBK. A. : "Multiple Bilateral Pulmonary Aspergillomata ," Thorex, 19: 104, 1964.

PUH"L, V ., ]EDUCKOV",

RIB LESIONS OF RHEUMATOID ARTHRITIS The pathogenesis of the rib destruction In rheumatoid arthritis Is not known. The possibility should be consIdered that one Is dealing with replacement of osseous tissue by either rheumatoid granulomas or fibrotic residues of rheumatoId Infiammatory process. Eight patients wIth severe, longstanding rheumatoid arthritis had definite erosions of the nonartlcular portions of the ribs. The posterIor aspects of the third, fourth and fifth ribs were Involved. When the lesion was small, It presented

as a cup-shaped excavation on the upper rib border. The rheumatoid lesion was also manifested as a localized nattenlng of the superior contour. thereby simulating the changes that may occur In paralytic poliomyelitis. In one Instance, complete destruction of a segment of the third rib mimicked malignant disease . ALPERl', M. "ND FBLD....N. F. : " Th e Rib Lesions of Rheumatoid Arthritis: ' Rlldiology, 82:872, 1964.

PATHOLOGY OF MESOTHELIOMATA A study of the pathology of 34 cases of prImary

tumors (meslotheJlomata) of the pleura and peritoneum shows these to be dIstinct and recognIzable neoplasms .whlch can be distinguished from primary carcinomata of the lung or other vIscera. The assoelation of these tumors with asbestos bodIes In lung tissue Is conllrmed. Many of the cases gave no his-

tory of Industrial exposure, and It Is possible that temporary or relatively trivial exposure may have occurred. HOURIHANE, D. O·B .: "Pathology of Mesotheliomata and an Analysis of their Association with Asbestos Exposure." ThorIIX, 19:268, 1964.