Thorax 1983;38:205-208

Pathogenic significance of Klebsiella oxytoca in acuterespiratory tract infectionJOAN T POWER, MARGARET-A CALDER

From the Department ofRespiratory Medicine and the Bacteriology Laboratory, City Hospital, Edinburgh

ABSTRACT A retrospective study of all Klebsiella isolations from patients admitted to hospitalwith acute respiratory tract infections over a 27-month period was carried out. Ten of theKlebsiella isolations from sputum and one from a blood culture were identified as Klebsiellaoxytoca. The clinical and radiological features of six patients are described. Four of these patientshad lobar pneumonia, one bronchopneumonia, and one acute respiratory tract infectionsuperimposed on cryptogenic fibrosing alveolitis. One of the patients with lobar pneumonia had a

small-cell carcinoma of the bronchus. We concluded that Klebsiella oxytoca was of definitepathogenic significance in these six patients and of uncertain significance in the remaining fivepatients. Klebsiella oxytoca has not previously been described as a specific pathogen in therespiratory tract. Close co-operation between clinicians and microbiologists in the managementof patients with respiratory infections associated with the Enterobacteriaceae is desirable.

Klebsiella oxytoca has not previously been describedas a specific respiratory pathogen. Bacillus oxytocawas first isolated by Flugge from a specimen of sourmilk in 1886.' 2 It was not until 1963 that the organ-ism was accepted as a member of the genus Kleb-siella and then only with reluctance on the part ofsome authorities.3 To define more clearly the role ofKlebsiella oxytoca as a pathogen in the respiratorytract we carried out a retrospective study of all Kleb-siella species isolated from sputum specimens andblood cultures of patients admitted to the respirat-ory and chest units of the City Hospital from June1979 to August 1981.

Methods

A total of 4800 patients were admitted during theperiod under review. About 12 000 specimens ofsputum were collected for culture and sensitivitytesting. A minority of patients had blood cultures.A Gram stain was made from the most purulent

part of the sputum. A sputum isolate of Klebsiellawas reported only if the organism was found withmany pus cells in the Gram film. A blood agar plateand a heated blood agar plate containing 10 units ofbacitracin per ml were inoculated and incubated in10% carbon dioxide for 18 hours. One McConkey

Address for reprint requests: Dr JT Power, Department ofRespiratory Medicine, City Hospital, Edinburgh EH10 5SB.

agar plate was inoculated and incubated for 18hours. The API 20E system (Analytal Product Inc)was used to identify the biochemical reactions. Thetwo biochemical reactions which differentiate Kleb-siella oxytoca from the Klebsiella pneumoniae organ-ism are its ability to liquify gelatin and its indolepositivity.The disc diffusion method was used to establish

antibiotic sensitivities. The following drugs weretested: ampicillin, chloramphenicol, co-trimoxazole,gentamicin, and tetracycline. Only one of the Kleb-siella oxytoca isolates was sensitive to ampicillin.

Results

There were 110 Klebsiella isolations from sputumand one from blood culture. Eleven of these organ-isms, including the one isolated from blood culture,were identified as Klebsiella oxytoca. This was iso-lated from 11 patients (eight men and threewomen). Their ages ranged from 46 to 80 years(mean 68). Four of the 11 patients had radiologicalevidence of lobar pneumonia and one of broncho-pneumonia. One patient had an acute respiratorytract infection superimposed on cryptogenic fibros-ing alveolitis and five had acute exacerbations ofchronic bronchitis.Ten patients fulfilled the Medical Research Coun-

cil's criteria for chronic bronchitis4 and one patienthad cryptogenic fibrosing alveolitis. One had dissemi-

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nated oat-cell carcinoma of the bronchus withsevere leucopenia caused by chemotherapy. Twopatients had undergone partial gastrectomy for pep-tic ulceration. One patient had maturity-onset diab-etes mellitus and one had chronic renal failure.Eight of the patients smoked 15-40 cigarettes a daywhile the remaining three were non-smokers. Onepatient had an excessive alcohol intake. In threepatients Klebsiella oxytoca appeared to play a part inthe pathogenesis of a slowly resolving pneumonia.

Case 1 A 46-year-old woman with a history ofchronic bronchitis presented with left-upper-lobepneumonia. Type 3 pneumococcal capsular antigenswere detected in both her sputum and her serum byimmunoelectrophoresis. Despite treatment with acombination of ampicillin and benzylpenicillin therewas no appreciable radiological improvement overher first two weeks in hospital, during which timeshe remained febrile. Over the first few days theupper lobe increased in volume and there was bulg-ing of the interlobar fissure (fig 1). During the thirdweek cavitation was noted in the area of consolida-tion (fig 2). Klebsiella oxytoca was subsequently iso-lated from her sputum. The organism was resistantto ampicillin and benzylpenicillin and her treatmentwas thus changed to an appropriate combination ofgentamicin and chloramphenicol. There followed agradual clinical and radiological improvement. Fib-reoptic bronchoscopy was carried out before herdischarge and the findings were normal. A chestradiograph taken three months later showedresidual fibrosis and loss of volume of the left upperlobe.

Case 2 A 55-year-old woman with a history ofchronic bronchitis also presented with consolidationof the left upper lobe. She had been started onampicillin and cloxacillin on the day before admis-sion. No pathogens were isolated from the initialsputum culture, although type 3 pneumococcal anti-gens were detected in both sputum and serum. Shewas treated with a combination of benzylpenicillin,ampicillin, and cloxacillin, with an initial satisfactoryclinical and radiological response. On her 10th dayin hospital her temperature rose to 38-50 C. At thisstage Klebsiella oxytoca was isolated from hersputum. As the organism was resistant to her anti-biotic regimen she was given a course of co-trimoxazole. She made an uneventful recovery,although again there was residual fibrosis in the leftupper lobe on a chest radiograph taken six monthsafter discharge from hospital.

Case 3 A 69-year-old man with a history ofchronic bronchitis presented with radiological evi-

Fig 1 A left lateral chest radiograph ofpatient 1 two weeksafter admission showing bulging of the interlobar fissure,evidence ofan increase in volume of the left upper lobe.

Fig 2 Chest radiograph ofpatient 1 two weeks afteradmission showing cavitation in the area of consolidationin the left upper lobe.

dence of right-upper-lobe pneumonia with abscessformation. Sputum culture on admission yielded a

profuse growth of Klebsiella oxytoca. He had notpreviously received antibiotics. Treatment was a

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Pathogenic significance of Klebsiella oxytoca in acute respiratory tract infection

Fig 3 Chest radiograph ofpatient 3 on admission showingconsolidation ofthe right upper lobe with abscessformation.

combination of ampicillin and co-trimoxazole; theorganism was sensitive to both drugs. As there wasno radiological improvement his antibiotic treat-ment was changed to a combination of benzyl-penicillin, gentamicin, and metronidazole during hissecond week in hospital. His condition deteriorated,however, and he died two weeks later. There was noevidence of bronchial carcinoma at necropsy.

Case 4 A 61-year-old man with a small-cell car-cinoma of the left-lower-lobe bronchus and distalleft-lower-lobe consolidation had bacteraemia dueto Klebsiella oxytoca. Eight days after his first courseof cytotoxic chemotherapy he developed pyrexia.His total white cell count was 0.2 x 109/l. Klebsiellaoxytoca was isolated from a blood culture. A mid-stream specimen of urine was sterile on culture.Despite treatment with a combination of gentami-cin, carbenicillin, and ampicillin he died the follow-ing day.

Case S A 72-year-old man with advanced cryp-togenic fibrosing alveolitis and cor pulmonale wasadmitted in type 2 respiratory failure (as defined byPao2 less than 8-0 kPa (60 mm Hg) and a Pco2above 6-7 kPa (50 mm Hg)5). This was precipitatedby an acute respiratory tract infection. He had takenampicillin before admission. Klebsiella oxytoca wasisolated from the initial sputum culture. He was nottreated for this infection as he died before the resultsof sputum culture were available. The organismshowed in vitro resistance to ampicillin. No post-mortem examination was carried out.

Case 6 An 80-year-old man was admitted with atwo-day history of confusion and of cough produc-tive of brown sputum. A chest radiograph showed aright pleural effusion and patchy inflammatoryinfiltrates throughout both lung fields. He had notreceived antibiotics before admission and treatmentwas started with ampicillin. Klebsiella oxytoca wasisolated from the initial sputum culture and so hisantibiotic treatment was changed to gentamicin andco-trimoxazole. He made no appreciable responseto treatment, however, and died on the fifth dayafter admission. There was no evidence of bronchialcarcinoma at necropsy.

The remaining five patients presented with acuteexacerbations of chronic bronchitis. They had noevidence of pneumonia on the chest radiograph.These patients had either been started on ampicillinbefore admission or responded to ampicillin, towhich the organism showed in vitro resistance. Itwas therefore difficult to assess the pathogenicity ofthe Klebsiella isolations.

Discussion

Acute pneumonia caused by Klebsiella species isuncommon. In most previously reported studies ithas accounted for only 1-2% of the organismsidentified in cases of acute pneumonia.6-8 Theexception was Tillotson's study, in which Klebsiellaspecies accounted for 8% of the isolations; buthis patients reflected the aged, debilitated popula-tion admitted to the medical wards of the BostonCity Hospital.9

Klebsiella oxytoca appeared to play a significantpart in producing a complicated lobar pneumonia inour first two patients. Both of these patients had aprimary type 3 pneumococcal pneumonia. In thecase of our first patient in particular, the course ofthe pneumonia resembled that of an acute klebsieliapneumonia rather than a pneumococcal pneumonia.Patient 3 had a pulmonary abscess in associationwith a Klebsiella oxytoca infection. His illness ran arelatively prolonged course. Klebsiella pneumoniacan cause an indolent pulmonary abscess10 but this isa relatively uncommon manifestation of the infec-tion. Likewise bronchopneumonia is unusual inassociation with acute klebsiella infection."'Acute klebsiella pneumonia most frequently

affects the upper lobes or the apical segments of thelower lobes. Three of our patients had an upper-lobe pneumonia. There were other radiological fea-tures suggestive of acute klebsiella pneumonia inour first six patients. An increase in volume of theaffected lobe with resultant bulging of the interlobarfissure and a tendency to abscess formation are fea-

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tures of acute klebsiella pneumonia which may aidin its differentiation from an acute pneumococcalpneumonia.'2 13 There is also a higher incidence ofpleural effusion and empyema formation in acuteklebsiella pneumonia. Patients 1 and 2 developedresidual parenchymal fibrosis, seen on the follow-upchest radiograph-another feature associated withacute klebsiella pneumonia.13

Bacteraemia reportedly occurs in 25% of cases ofacute klebsiella pneumonia.11 Klebsiella oxytoca was

of undoubted pathogenic significance in patient 4, inwhom it was isolated from a blood culture. Theorganism was very unlikely to have been a con-

tamninant as there was a pure growth on culture andthere were compatible clinical features.The high incidence of concurrent diseases in our

patients is of interest. Chronic bronchopulmonarydiseases, alcoholism, and to a lesser extent diabetesmellitus have long been recognised as predisposingpatients to acute klebsiella pneumonia'3 and itwould appear that this is true of Klebsiella oxytocainfections.The role of the Enterobacteriaceae may be

difficult to interpret in a clinical context. Not every

Gram-negative bacillus in the sputum is a pathogen.Some are commensals and some appear during or

after chemotherapy. When these organisms are iso-lated from a culture a Gram film should also bestudied and the two examinations assessed together.When many bacilli are seen in association with largenumbers of pus cells the organism is more likely tobe of pathogenic significance. The importance of thebacteriological findings must always be assessed inrelation to the patient's clinical condition. Closeco-operation between the laboratory and cliniciansis essential. The presence of an organism that isuncommon in the respiratory tract poses an addi-tional problem. We have concluded, however, on

the basis of our observations in this study that Kleb-siella oxytoca is a potentially significant pathogen inthe respiratory tract. It was most likely the primaryinfecting agent in four patients and caused a

significant secondary infection in two patients withpneumococcal lobar pneumonia. When Klebsiella

oxytoca is isolated from a patient who is failing torespond to current treatment or whose condition isdeteriorating it should be treated aggressively withappropriate antibiotics.

We are grateful to Professor DC Flenley and DrNWHome for permission to include their patients in thisstudy. We would also like to thank the staff of thebacteriology laboratory at the City Hospital fortechnical assistance and Miss Sheila Black for typingthe manuscript.

References

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3Cowan ST, Steel KJ. Manual for the identification ofmedical bacteria. 2nd ed. Cambridge: Cambridge Uni-versity Press, 1974:111.

4 Medical Research Council. Definition and classificationof chronic bronchitis. Lancet 1965;i:775-9.

s Flenley DC. Respiratory medicine. London: BalliereTindall, 1981:123.

6Bath JCL, Boissard GPB, Calder MA, Moffat MAJ.Pneumonia in hospital practice in Edinburgh 1960-1962. Br J Dis Chest 1964;58:1-16.

Sullivan RJ jun. Dowdle WR, Marine WM, HierholzerJC. Adult pneumonia in a general hospital. ArchIntern Med 1972;129:935-42.

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9 Tillotson JP, Finland M. Bacterial colonisation and clini-cal superinfection of the respiratory tract complicatingantibiotic treatment of pneumonia. J Infect Dis1969;119:597-624.

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l Pierce AK, Sanford JP. Aerobic Gram negative bacillarypneumonias. Am Rev Respir Dis 1974;110:647.

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