J Neurosurg 47:228-235, 1977

A prospective study of traeheobronchial bacterial flora in acutely brain-injured patients with and without antibiotic prophylaxis HEWITT C. GOODPASTURE,M.D., DONALD A. DOUGLAS W. VOTH, M.D., CmEN LIU, M . D . ,

ROMIG, M.D.,

AND CHARLES E. BRACKET'f, M . D .

Head Trauma Unit, Section of Neurosurgery, Department of Surgery, and Division o f lnfectious Disease, Department of Medicine, University of Kansas School of Medicine, Kansas City, Kansas The authors observed prospectively 28 brain-injured patients, who required respiratory tract intubation, to determine the effect of antibiotic prophylaxis on bacterial flora, the rate of flora change, and the appearance of infection. Antibiotics not only failed to alter the rate of abnormal colonization but were associated with an earlier appearance of Gram-negative bacilli, the organisms that produced the most severe infections. Although more infections occurred in patients initially untreated with antibiotics, these infections were usually mild and caused by organisms susceptible to highly effective and relatively safe drugs. Although highly reproducible as a laboratory determination, the nitroblue tetrazolium dye test score showed no consistent relationship with the presence or absence of bacterial infection. Regular and extensive clinical and laboratory observations, including cultures of the respiratory tract, helped to make the antibiotic administration in these patients specifiC, appropriate, and reasonable. Broad spectrum antibiotic prophylaxis does not prevent and may enhance the development of severe pulmonary infection in these patients. KEY W O R D S tracheostomy 9 chemoprophylaxis 9 antibiotics nitroblue t e t r a z o l i u m 9 brain injury 9 p u l m o n a r y infection 9

p

ULMONARY infection is a major cause of m o r b i d i t y and mortality in patients hospitalized for treatment of severe t r a u m a and especially those with brain injury. 6,8,x9 M a n y brain-injured patients require prolonged tracheal intubation as well as v e n t i l a t o r y a s s i s t a n c e with m e c h a n i c a l devices. U n d e r such conditions, the upper b r o n c h i a l tree b e c o m e s colonized with bacteria n o r m a l l y found in the posterior n a s o p h a r y n x . In certain situations, the flora resident in the pharynx and trachea is often replaced by bacteria potentially pathogenic to

228

9

the r e s p i r a t o r y tract, t~,~9,23 All of the mechanisms of these changes in site and character of flora have not been identified, but occult aspiration has been documented, 3 and s o m e studies have i n c r i m i n a t e d nosocomial reservoirs. *,~5,~ In addition, the complex alveolobronchiolar clearance dynamics 9 m a y be adversely affected by tracheal intubation with or without previous acute brain injury? ,~9 Such c o l o n i z a t i o n m a y precede the development of severe infection or, conversely, m a y have no recognized clinical

J. Neurosurg. / Volume 47 / August, 1977

Antibiotics and pulmonary infections significance. Since fever, leukocytoses, abnormal chest roentgenograms, and bronchorrhea may be produced by acute brain injury alone, differentiation between the "colonized" and the "infected" state may be difficult. Prophylactic antibiotics are often employed, presumably to prevent pneumonia, although many investigators have questioned their value. 1,7,14,18

Between 1968 and 1973, 108 acutely braininjured patients were studied in a two-bed Head Trauma Unit (HTU) at the University of Kansas Medical Center. We used a comprehensive clinical and bacteriological monitoring system described earlier. TM We are reporting here prospective observations of the tracheobronchial bacterial flora of 28 of these patients, some of whom received antimicrobials and all of whom required prolonged tracheal intubation. The nitroblue tetrazolium (NBT) dye test was evaluated as a means of distinguishing respiratory tract bacterial colonization from infection following acute brain injury. Materials and Methods

The 28 patients in this analysis met the following criteria: 1) no evidence of respiratory tract infection on admission; 2) support of respiration with mechanical devices for at least 48 hours; and 3) tracheal intubation with respiratory tract flora monitoring for at least 7 days. In all 28, tracheal or bronchial aspirates (using fiberoptic bronchoscopy) and blood specimens were obtained on Days 1, 2, 3, 5, and 7; all but three of these patients were also studied on Days 10, 14, and 21. In each instance chest x-ray films and complete blood counts were obtained at 24- to 48-hour intervals during the first 10 days in the HTU. Equipment for respiratory assistance and nebulizers, if used, were cultured on Days 1, 3, 7, and at weekly intervals thereafter. In 15 patients, blood was obtained daily for assay of NBT reduction. Extensive detailed observations of the neurological and cardiorespiratory systems, body temperature, and fluid and electrolyte intake and output were performed either continuously or several times daily. The recovery of alpha and gamma streptococci, diphtheroids, Neisseria catarrhalis, and coagulase-negative staphylococci from the upper bronchial tree under conditions of tracheal intubation was usual at the time of J. Neurosurg. / Volume 47 / August, 1977

admission to the HTU, and was considered "normal." A predominance of any other organism recovered from respiratory tract sites was defined as "abnormal." "Change in flora" was defined as replacement of the initial predominant organism with another. Details of culture techniques have been published previously.TM The criteria utilized to establish presence of a bacterial respiratory tract infection were either of the following: 1) the recovery of the same organism from the blood and respiratory secretions (three instances), or 2) the visualization of acutely inflamed exudative bronchial mucosa seen directly by bronchoscopy and the isolation of pathogenic organisms from the bronchial tree (13 instances). Although fever, leukocytosis, rales, rhonchi, and pulmonary infiltrates were usually present during the initial 72 hours following head injury, these clinical parameters were not considered diagnostic by themselves. Moreover, the diagnosis of bacterial respiratory infection was established only when the observations of either D.A.R. or H.C.G., who followed each patient and monitored the bacterial flora, agreed with the independent observations of the physician responsible for the patient's care (C.E.B.). "Severe" infection occurred if the above criteria for bacterial respiratory tract infection were met, plus the development of septicemia or pulmonary infiltrates, rales, and a pO~ of less than 60 mg Hg. Each of these clinical parameters was verified by multiple routine and standard observations. "Superinfection" was defined as the development of an acute increase in the inflammatory exudative reaction of the bronchial mucosa associated with presence of a new predominant pathogenic organism. At the outset of the study, patients admitted to the HTU were given intravenous prophylactic antibiotics if it appeared that intubation would be required for more than 24 hours (Group 1:16 patients). Subsequently, patients were given antimicrobials only when the diagnosis of respiratory tract infection had been made according to the above criteria (Group 2:12 patients). Results

Table 1 presents comparative data on the two groups of patients. The groups were not significantly different (Student's t-test) in 229

H. C. TABLE 1

TABLE 3

Characteristics of two groups of patients with acute brain injury

Predominant pathogens recovered by 48 hours after brain injury*

Characteristic no. of cases age:l: male/female days studied:[: days on respirator~ days intubated~

Group 1" Group 2t 16 28.6 12/4 12.2 2.8 10.9

Total

12 33.9 9/3 13.9 3.3 11.7

28 30.2 21/7 12.3 3.1 11.0

*Prophylactic antimicrobials given: ampicillin (2 gm/day intravenously), or cephalothin (4 gin/day intravenously) to 11 patients; cephalothin (4 gm/day intravenously) and gentamicin (3 mg/kg/day intravenously) to five patients. tNo prophylactic antimicrobials given. ~tMean values. None of the differences between groups were significant by Student's t-test.

relation to the number of patients and days studied, m e a n age, sex, days intubated, and days on the respirator. Bacterial Flora

T a b l e 2 shows the changes in the predominant bacterial flora during the initial 48 hours of intubation. Seventeen (61%) of the 28 patients s h o w e d bronchial flora change. Although the frequency of flora change was slightly m o r e in Group 2, the difference was not statistically significant; it is interesting that none o f the Group 2 patients received antibiotics during that time. Table 3 lists organisms recovered from the 17 patients from both groups who had b e c o m e colonized with pathogens within 48 h o u r s . T e n o f the 17 patients were p r e d o m i n a n t l y colonized by Gram-positive organisms; seven of these 10 were Group 2 patients. Conversely, six of seven patients who were colonized with Gram-negative rods

TABLE 2 Predominant tracheobronchial flora observed by 48 hours after brain injury

Predominant Flora Recovered

Group 1 Patients

Group 2 Patients

Total No. 7o

pathogenic normal total

9 7 16

8 4 12

17 61 11 39 28 100

230

Goodpasture, et

Organism Gram-positive

Staph. aureus St. pyogenes

Group 1

Group 2 Total

3

5

(Group A)

0

1

(Group B) Gram-negative

0

1

total

3 1 1 1 0

9

0 0 0 0 1

St. pyogenes

K. pneumoniae E. aerogenes P. aeruginosa E. coli H. influenzae

al.

8

10

17

*Infection occurred in no patients in Group 1 and in two patients in Group 2 by 48 hours of intubation. were Group 1 patients. These associations between patients' groups and flora recovered were significant at the p < 0.05 level. In the period between 48 hours and 7 days, six m o r e patients b e c a m e a b n o r m a l l y colonized, making a total of 23 patients (Table 4). The frequency of colonization with pathogens was high in both groups; the change in Group 1 was slightly higher but not statistically different (88% versus 75%) from Group 2. However, four of five of the Grampositive isolates were from Group 2 patients, and 13 of 18 Gram-negative isolates were from G r o u p 1 patients; again, these associations were significant at the p < 0.05 level. Pseudomonas Colonization

Twenty-five patients (14 in Group 1 and 11 in Group 2) were studied for 10 days or longer. P s e u d o m o n a s aeruginosa, found in 13 of these patients, was the most common tracheobronchial colonizer by the tenth day. Table 5 shows the relationships between the time and appearance of P. aeruginosa as the predominant organism of the respiratory tracts of patients in the two groups. The frequency of colonization with this organism was closely comparable (seven of 14 in Group 1 and six of 11 in Group 2). The mean day of colonization for pseudomonas (the mean day at which pseudomonas was first identified as the predominant organism), was slightly higher in Group 2 patients; this indicated a J. Neurosurg. / Volume 47 / August, 1977

Antibiotics and pulmonary infections TABLE 4

TABLE 6

Predominant pathogens recovered on the seventh day after brain injury*

Respiratory infection frequency in patients during 14 days o f observation

Organism Gram-positive

Group 1

(Group A) Gram-negative

0

1

5 3 2 2 1

2 0 2 1 0

Staph. aureus St. pyogenes

1

P. aeruginosa E. aerogenes K. pneumoniae P. mirabilis E. coli

total

14

Group 2 Total 5 3

9

18

23

*Infection occurred in two patients in Group I and in nine patients in Group 2 by 7 days.

longer interval before colonization with pseudomonas in patients who did not receive prophylactic antibiotics. The difference was not significant at p < 0.05 by Student's t-test analysis. Reservoir Surveillance

Scant amounts of E. coli and Klebsiella p n e u m o n i a e were recovered from a side arm

nebulizer on one occasion, and small numbers of P. aeruginosa were recovered from one humidifier. In neither instance was this a s s o c i a t e d with r e c o v e r y o f these s a m e organisms from the bronchial tree of the patient.

Infections

Based on a 14-day follow-up study, colonization with pathogenic Gram-positive TABLE 5 Tracheobronchial colonization with pseudomonas 10 days after brain injury*

Group 1 no. patients at risk no. patients colonized mean day of colonizationt

14 7 6.7~t

Group 2 Total 11 6 8.5~t

25 13 7.7

*Infection with pseudomonas had occurred in two of these patients by the tenth day. tMean day of colonization with pseudomonas as the predominant organism. ~tt = 0.95 (p = 0.4). J. Neurosurg. / Volume 47 / August, 1977

Category

Group 1

no. at risk no. of infected no. infected/no, at risk mean day of diagnosis organisms

9 5 0.56 8.4

E. aerogenes K. pneumoniae P. aeruginosa Staph. aureus St. pyogenes

(Group A)

St. pyogenes

(Group B)

H. influenzae

Group 2 Total 11 9 0.82 4.9

20 14 0.70 6.1

2 1 1 1

0 1 1 4

2 2 2 5

0

1

1

0

0

1

1

1

1

cocci was followed by infection in 88% o f the patients; in contrast, G r a m - n e g a t i v e bacilli produced infection in 58% of colonized patients. T a b l e 6 presents infection a t t a c k rates and the m e a n day of diagnosis by patient group and lists the o r g a n i s m s implicated. Fourteen patients had at least one bacterial respiratory infection while in the H T U . Although the rate of infection was greater and occurred earlier in G r o u p 2 patients, the differences were not statistically significant. The o r g a n i s m s implicated were S t a p h y l o c o c c u s a u r e u s and G r o u p A or B streptococcus in seven o f 10 G r o u p 2 infections; enteric G r a m - n e g a t i v e rods caused disease in only two instances, despite colonization in nine patients. F o u r of the five infections diagnosed in G r o u p 1 patients were caused by G r a m - n e g a t i v e rods. Infection in five o f the 14 patients (36%) was severe according to the criteria o f our study; three patients were in G r o u p 2 and two were in G r o u p 1. H o w e v e r , two of the three G r o u p 2 i n f e c t i o n s were c a u s e d by P. aeruginosa superinfections that developed after successful t r e a t m e n t o f staphylococcal bronchopneumonia. One patient in each group died f r o m complications of infection, an overall case fatality ratio of 14%. It is i m p o r t a n t to note that G r a m - n e g a t i v e bacilli caused all five of the severe infections observed; two patients developed septicemia and three others had m a r k e d c o m p r o m i s e o f respiratory function f r o m p n e u m o n i a . It is interesting that over 60% of the G r a m - n e g a t i v e 231

H . C. G o o d p a s t u r e , TABLE 7 Serial nitroblue tetrazolium scores in seven patients with bacterial respiratory infection*

Nitroblue Tetrazolium Scores (7o) Case No. 1

2 3 4 5 6 7 mean SD

Day Day Days after before Infection Antibacterial Treatment Infection Diagnosed 1 2 3 15 42 6 7 60 95 35 26 8 32.7 27.9

15 7 3 11 80 95 72 31 55 41.3t 33.2

2

4 6 2 19 35 21 33 8 14.4t 12.3

6

6 11 4 15 32 18 19 3 12.7 8.8

11

2 5 1 4 43 15 11 2 10.4 12.4

*Cases 3 and 5 had two separate bacterial infections. ~Difference significant at p

A prospective study of tracheobronchial bacterial flora in acutely brain-injured patients with and without antibiotic prophylaxis.

J Neurosurg 47:228-235, 1977 A prospective study of traeheobronchial bacterial flora in acutely brain-injured patients with and without antibiotic pr...
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