Anaerobic pleuropulmonary infections

Clinical considerations

Anaerobic infections are undoubtedly the most commonly overlooked of all bacterial infections. This is the case in pleuropulmonary infections, Sydney M. Finegold, M.D.* particularly when specimens for anaerobic culture John G. Bartlett, M.D.f usually are not obtained and standard micro- biologic techniques often are inadequate. The purpose of this paper is to discuss a few of the clinical problems associated with anaerobic pleuropulmonary infections, to mention tech- niques for collection of materials for proper cul- ture of anaerobic pulmonary pathogens, and to consider briefly the spectrum of pulmonary dis- eases produced by anaerobes based on our recent experiences. Figure 1 is the posteroanterior chest roentgeno- gram of a 67-year-old man who had just been ad- mitted to the hospital with an extensive necrotiz- ing involving much of the left lung. There was apparently an empyema at the right base as well, but numerous attempts at recovering fluid from this area by thoracentesis were unsuc- cessful. Coughed sputum culture yielded Pseudo- monas aeruginosa in heavy growth. The house of- ficer questioned this laboratory report, since this • Department of Medicine, Wads- worth Veterans Hospital, and the patient had not been hospitalized previously, and University of California Medical it would be most unusual for someone to come Center, Los Angeles, California. into the hospital with an extensive necrotizing f Infectious Disease Section, Veter- pneumonia due to P. aeruginosa in the absence of ans Administration Hospital, Sepul- any severe underlying disease. Furthermore, the veda, California and the University of California Medical Center, Los patient had been chronically ill for 6 months and Angeles, California. had lost 27.3 kg before becoming acutely ill and

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Fig. I. Chest roentgenogram showing necrotizing pneumonia involving left lung. seeking hospitalization. Again, this is oratory report, he undoubtedly would not the clinical picture of Pseudo- have died, inasmuch as anaerobes typi- monas pneumonia. In addition, this cally are resistant to aminoglycosides. patient was an alcoholic and thus This case is not an unusual one. might well have aspirated and was Among 70 patients with documented bringing up foul-smelling sputum, a anaerobic pulmonary infection, there sure indication that anaerobes must be were 23 instances of potential aerobic involved in the process. Accordingly, pathogens (Staphylococcus aureus, 7; a transtracheal aspiration was done to P. aeruginosa, 7; Diplococcus pneumo- bypass the indigenous flora of the niae, 9; Klebsiella-Enterobacter, 2; mouth and upper respiratory tract. Escherichia coli, 4; Haemophilus influ- This specimen yielded no P. aerugi- enzae, 3) recovered from expectorated nosa, but instead six different anaer- sputum, but not found on trans- obic organisms, all in high counts. tracheal aspiration or in material oth- Had the patient been treated with gen- erwise more directly collected. Figure tamicin on the basis of the original lab- 2 shows that there are significant

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of author. Hoeprich PD: Etiologic diagnosis of lower respiratory tract infections. Calif Med 112: 1-8, 1970.) numbers of both aerobic and anaerobic bacteria in the mouth and upper respi- ratory passages, and further empha- sizes the necessity of bypassing such areas of normal flora in order to docu- ment accurately the nature of pulmo- nary infection. This is particularly true in the case of suspected anaerobic in- fection. Transtracheal aspiration1 is perhaps best performed through the cricothyroid membrane. Figure 3 shows a transtracheal aspiration being per- formed on a patient. The polyethylene tube has been inserted through the needle into the trachea. The needle has been withdrawn and the specimen is now being obtained by the use of Fig. 3. Photograph showing transtracheal as- suction and a Luken's trap. piration. A second important consideration for the clinician attempting to docu- such specimens will die after relatively ment the presence of anaerobes in pul- brief exposure to air, it is important monary infection is proper transport that the material be placed under an- of the specimen. Since anaerobes in aerobic conditions as soon as possible.

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type of infection. With the use of trans- tracheal aspiration, diagnosis was pos- sible even in the absence of empyema and cases could be diagnosed earlier— before development of or em- pyema. Table 2 shows the predisposing conditions in the 100 cases. The two major predisposing factors were aspi- ration, usually related to altered con- sciousness, and . A Fig. 4. Photograph of gassed-out tube with detailed breakdown of the culture butyl rubber stopper.

Figure 4 illustrates a tube which has been gassed out with oxygen-free gas m -0%—"— and stoppered with a butyl rubber stopper. The specimen is injected 1 through the stopper into the anaerobic WS———s — atmosphere and the tube is then capped. Another suitable and less ex- pensive transport technique is shown in Figure 5. Plastic disposable syringes Fig. 5. Photograph of syringes containing with tight-fitting plungers are suitable exudate, with rubber stoppers on needles to for transport purposes. All air is ex- preserve anaerobic conditions. pelled from the syringe and needle, and the needle is then capped with a Table I. Anaerobic pleuropulmonary rubber stopper as for arterial blood gas disease; types of infection measurements. With this transport setup, it is important that the speci- No. of cases men be received in the laboratory 1958- 1969- within 20 minutes. 1968 1972

We consider here the picture of an- Pulmonary with- 6 20 aerobic pleuropulmonary infection as out empyema illustrated by the first 100 cases that Pulmonary abscess with 4 2 we have studied.2 In Table 1, these empyema Necrotizing pneumonitis 7 10 cases are listed in terms of the type of without empyema pulmonary involvement and in two Necrotizing pneumonitis 6 1 time periods. During the earlier time with empyema period, transtracheal aspiration was Empyema without abscess 20 8 seldom used and empyema fluid was Pneumonitis without em- 0 15 pyema or abscess the most common source of material Infected bronchogenic 1 0 for establishing this diagnosis. Thus, carcinoma cavity the cases documented between 1969 and 1972, when transtracheal aspira- tion was used commonly, more accu- Total 44 56 rately reflect the true picture of this Total with empyema 30 11

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Table 2. Anaerobic pleuropulmonary melaninogenicus) were disease; predisposing conditions particularly common. However, Bac- (100 cases) teroides fragilis was also present in 21% of cases. Figures 6 and 7 show the No. of cases microscopic morphology of F. nuclea-

Aspiration tum and B. melaninogenicus, respec- Altered consciousness 63 tively. Anaerobic and microaerophilic Dysphagia 5 streptococci and cocci were also seen Intestinal obstruction 5 with some frequency in these infec- Preceding anaerobic infection tions. Anaerobic gram-positive bacilli Periodontitis 30 Intraabdominal 6 and Clostridia were less commonly en- Local underlying conditions countered. Potential aerobic pathogens Bland pulmonary infarction 9 were recovered from one third of these Bronchogenic carcinoma 7 cases. Despite the presence of these aer- Bronchiectasis 6 obic pathogens, quantitative aspects of Systemic underlying condition 13 None apparent 15 the bacteriology as well as distinctive clinical features indicated that these infections were anaerobic in origin. sources utilized in the diagnosis of Symptoms were commonly present 2 to these cases is noted in Table 3. Distinc- 4 weeks prior to therapy when abscess tive clinical features which suggested formation or empyema was part of the the possibility of anaerobic pulmonary clinical picture (Table 5). Cases with infection in these 100 cases were pul- only pneumonitis had a much shorter monary parenchymal necrosis (70 duration of symptoms prior to therapy cases), subacute or chronic presenta- and were undoubtedly treated before tion (57 cases), suspected aspiration (74 they had an opportunity to develop cases), and putrid discharge (53 cases). these complications. Note in Table 5, Only the putrid discharge is virtually also, that fever persists for some time specific, although one must keep in after therapy has been instituted, par- mind that odor may be imparted to ticularly in the case of empyema. In sputum from anaerobic processes such as in the mouth. Parenchy- mal necrosis is not specific for anaero- Table 3. Anaerobic pleuropulmonary bic infection, but is commonly seen in disease; culture sources this condition. Subacute or chronic (100 cases)

presentation of the illness, noted in al- No. of cases most two thirds of the cases, is unusual for bacterial pulmonary infections Pleural fluid 40 (7)* other than tuberculosis or mycotic in- Percutaneous transtracheal 57 (2) aspirate fections. Percutaneous transthoracic 1 The results of bacteriologic studies aspirate in these 100 cases are listed in Table 4. Thoracotomy specimen 5 (2) Anaerobic gram-negative bacilli were Blood culture 2 (2) the most common anaerobes encoun- Distant metastatic site 1 Autopsy material 2 (1) tered and two anaerobic gram-negative bacilli (Fusobacterium nucleatum and * Two or more sources yielded anaerobes.

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Table 4. Anaerobic pleuropulmonary disease; bacteriologic results (100 cases)

Organism isolated Organism in pure isolated culture No. of No. of cases cases

Anaerobic gram-negative bacilli Fusobacterium nucleatum 34 6 F. necrophorum 1 0 Fig. 6. Photomicrograph of Gram-stain smear Bacteroides melanino- 31 1 of a pure culture of F. nucleatum. genicus B. fragilis 21 2 B. oralis 16 0 the latter case, this undoubtedly re- B. pneumosintes 1 0 flects inadequate early drainage. The Unidentified 10 0 mortality is generally low, except in Anaerobic gram-negative cocci the cases of necrotizing pneumonia Veillonella 7 0 where it was 25%. Anaerobic gram-positive We studied 26 cases of lung abscess. cocci Criteria for inclusion as a case of lung Microaerophilic strep- 26 12 tococcus abscess included a pulmonary cavity at 19 3 least 2 cm in diameter on roentgeno- Peptococcus 15 0 gram, availability of a pretreatment Anaerobic gram-positive transtracheal aspirate for culture, and bacilli Propionibacterium spe- 9 0 absence of any other potential cause of cies pulmonary cavitation (hematogenous Eubacterium species 5 0 infection, tuberculosis, nonbacterial Bifidobacterium 3 0 disease). The location of the abscess by Unidentified catalase- 10 1 negative nonsporu- lateral chest roentgenogram is noted lating in Figure 8. Most of the abscesses oc- perfringens 5 2 curred in dependent segments, either Clostridium species 2 0 the posterior segments of the upper Concurrent aerobic po- 33 0 tential pathogens lobes or the superior segments of the Staphylococcus aureus 9 0 lower lobes or other dependent lower Pseudomonas aeruginosa 7 0 lobe segments. Anaerobic organisms Escherichia coli 7 0 only were isolated from 16 cases; only Klebsiella-Enterobac- 6 0 ter two had aerobic isolates alone; in eight Proteus species 4 0 patients both anaerobic and aerobic Diplococcus pneumoniae 4 0 organisms were recovered. Haemophilus influenzae 3 0 Our bacteriologic studies in 79 cases Pseudomonas maltophilia 1 0 Eikenella corrodens 1 0 of empyema (excluding cases of post- Group A beta-hemo- 1 0 operative empyema) also establish that lytic streptococcus this disease is primarily anaerobic in Providencia 1 0 etiology. Only 17 cases (22%) yielded

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Fig. 7. Photomicrograph of Gram-stain smear of a pure culture of B. melaninogenicus.

Table 5. Anaerobic pleuropulmonary disease; clinical features (100 cases)

Necrotizing Abscess pneumonia Pneu- without and Empy- monitis empyema empyema ema only Series

Cases (no.) 26 24 41 15 100 Duration of symptoms prior to therapy 4* 2 4 0.5 3.5 (wk) Duration of fever after therapy (wk) 1 1.8 4 0.3 2.5 Duration of infection after therapy (wk) 8 15 20 3 13 Mortality It 6 5 3 14

* Median duration in weeks, f Total cases. aerobic organisms exclusively; the re- have a predisposition to aspiration, maining 62 cases (78%) yielded anaer- and if a reliable pretreatment culture obes, either with aerobes, 24 cases specimen was available (transtracheal (30%), or without aerobes, 38 cases aspirate, empyema fluid, or positive (48%). blood culture) in the presence of in- We studied 70 patients with aspira- fection in a dependent pulmonary seg- tion pneumonia, included only if they ment. Pneumonitis alone was present were observed either to aspirate or in 38 cases, whereas 20 had a definite

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mon isolates. Anaerobic gram-positive Anterior bacilli were seen relatively uncom- monly. A variety of aerobic or faculta- tive bacteria was recovered as well. Of particular interest is the breakdown of cases noted in Table 7. Among the 38 patients whose was acquired in the community, there were only three who yielded aerobes

LOCATION OF ABSCESS ON LATERAL CHEST X-RAY Table 6. Aspiration pneumonia; (26 cases) bacteriology (70 cases) Fig. 8. Graphic representation of location of lung abscesses. No. of cases

abscess and 12 had a necrotizing pneu- Anaerobic gram-negative monia. In these groups empyema was bacilli also present in five, two, and one pa- Bacteroides melaninogenicus 27 (1) B. jragilis 10 (1) tients, respectively. The major predis- B. oralis 9 posing causes for aspiration were com- B. corrodens 2 promised consciousness in 67 cases B. pneumosintes 1 (alcoholism, 23; cerebrovascular acci- Fusobacterium nucleatum 19 dent, 13; seizure disorder, 9; general F. necrophorum 1 Unidentified anesthesia, 9; drug ingestion, 8; miscel- 4 (1) Anaerobic cocci laneous, 5) and dysphagia in nine cases Peptostreptococcus 23 (5) (neurologic disorder, 7; esophageal Peptococcus 11 (1) stricture, 2). Transtracheal aspirates Microaerophilic streptococ- 9 (1) were the primary source for bactério- cus logie diagnoses (63 cases), although Veillonella 4 Anaerobic gram-positive bacilli eight pleural fluids and four blood cul- Eubacteria 6 tures yielded diagnostic results. The Propionibacteria 6 reasons that blood cultures are not Bifidobacteria 2 often positive in patients with anaero- Clostridia 2 bic pleuropulmonary disease are not Aerobic gram-positive cocci 11 clear. Only nine cases yielded aerobic Streptococcus pneumoniae (2) Staphylococcus aureus 11 (2) pathogens only. Thirty-two of the 70 Enterococcus 3 cases yielded anaerobes exclusively, Group A beta-hemolytic 2 whereas 29 patients had both groups of streptococci pathogens recovered. The specific bac- Aerobic gram-negative bacilli tériologie findings are noted in Table Klebsiella sp 8 (2) Pseudomonas aeruginosa 7 6. Anaerobic gram-negative bacilli and Escherichia coli 6 anaerobic cocci of various types again Enterobacter cloacae 4 were the predominating organisms. Haemophilus influenzae 2 Among the gram-negative anaerobic Citrobacter freundi 1 rods, once more B. melaninogenicus Pseudomonas maltophilia 1 and F. nucleatum were the most com- * Recovered in pure culture.

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Table 7. Aspiration pneumonia; the man had diabetes, and diabetics microbiology are known to be more prone to anaero- bic and certain other types of infection than the general population. Second, the infection was in a dependent seg- onl y case s onl y an d aerobe s No . o f Anaerobe s Aerobe s Anaerobe s

Hospital acquired 32 7 6 19 Community ac- 38 25 3 10 quired alone, and 25 of the 38 had anaerobes to the exclusion of other types of or- ganisms. The picture is distinctly dif- ferent in hospital-acquired aspiration pneumonia. Among the 32 cases of this type in the study, there were six pa- tients with aerobes alone and only seven with anaerobes alone, whereas 19 had mixtures of aerobes and anaer- obes. This reflects the fact that hospi- talized patients become colonized with certain opportunistic pathogens from the hospital environment, such as S. aureus and various facultative gram- Fig. 9. Roentgenogram of the chest on admis- sion showing infiltrate in left lung field. negative bacilli. These organisms may then be aspirated, along with anaer- obes, if aspiration occurs in the hospi- tal setting. This is an important con- sideration in establishing appropriate treatment regimens. One case further illustrates some of the points under discussion. A 53-year- old engineer with a history of diabetes mellitus and mild emphysema had what he thought was a chest cold. When this persisted for 3 weeks, he sought attention at our hospital. The admitting posteroanterior chest roent- genogram showed an infiltrate in the left mid-lung field (Fig. 9). This infil- trate was in the superior segment of the left lower lobe (Fig. 10). The house officer considered the possibility of an- aerobic infection in this patient on the Fig. 10. Lateral roentgenogram of chest on day of admission revealing that infiltrate is in basis of several kinds of evidence. First, superior segment of left lower lobe.

Downloaded from www.ccjm.org on September 26, 2021. For personal use only. All other uses require permission. 110 Cleveland Clinic Quarterly Vol. 42, No. 1 ment suggesting the possibility of aspi- sent to the laboratory, and aerobic and ration, although there was no history anaerobic cultures were requested. obtainable of a period of unconscious- The laboratory reported "no growth." ness or frank aspiration. Third, the ill- The patient had not been treated in ness was of subacute onset which is one the interim, inasmuch as he was not of the clues to anaerobic pulmonary in- particularly sick and the physician in fections cited previously. In addition, charge of the case was anxious to es- the patient was noted to have definite tablish the specific diagnosis. The case periodontal disease. Finally, he had a was then reviewed and the original history of postnasal discharge which posteroanterior chest roentgenogram had a foul odor, presumably reflecting was considered possibly to show a left chronic involving anaerobes. hilar mass. Accordingly, a workup for The house officer, being aware of the possible carcinoma of the lung was un- fact that conventional, coughed spu- dertaken. During the course of this tum culture would not be suitable to workup, one day the patient mani- diagnose an anaerobic pulmonary in- fested focal Jacksonian seizures on the fection, proceeded to do a transtra- left. Brain scan and arteriography cheal aspiration. Recognizing the need demonstrated a cerebral mass lesion. to place the specimen under anaerobic At neurosurgical exploration, a large conditions promptly, he did this using abscess containing 40 cc of foul-smell- a gassed-out tube. The specimen was ing pus was encountered and drained.

Fig. 11. Gram-stain smear of material from .

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error, and that the technique in the laboratory was inadequate for growth of anaerobes at that time. Summary and conclusions Anaerobic bacteria, alone or with aerobic organisms, are commonly in- volved in the pathogenesis of aspira- tion pneumonia, primary lung abscess, and pleural empyema. Failure to col- lect, transport, and culture infectious materials by appropriate anaerobic techniques may forfeit the diagnosis of anaerobic pleuropulmonary infection. Transtracheal aspiration of bronchial secretions circumvents contamination of bronchopulmonary exudates by members of the indigenous anaerobic Fig. 12. Gram-stain smear of material ob- oropharyngeal flora. It is imperative tained from repeat transtracheal aspiration. that a Gram-stained smear of each specimen be obtained, so that the effi- Direct Gram stain of the material from ciency and accuracy of culture results this abscess showed thin, pale-staining can be compared with the microscopic filamentous rods which were gram- examination, and so that the physician negative (Fig. 11). This was presumed immediately has a preliminary idea of to be Fusobacterium (and ultimately the nature of the pleuropulmonary was grown out and confirmed as F. nu- pathogens. cleatum). At this point, the transtra- cheal aspiration was repeated and simi- References lar organisms were noted on direct 1. Bartlett JG, Rosenblatt JE, Finegold SM: Gram stain of this material (Fig. 12). Percutaneous transtracheal aspiration in This case emphasizes the importance the diagnosis of anaerobic pulmonary infec- tion. Ann Intern Med 79: 535-540, 1973. of the Gram stain. Had it been done 2. Bartlett JG, Finegold SM: Anaerobic pleu- originally it would have been apparent ropulmonary infections. Medicine 51: 413- that the original culture report was in 450, 1972.

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