Effect of intensive care unit nosomial pneumonia on duration of stay and mortality

EI’MF

RlWORTS

t of intensive care unit ia on al -prMw of stay and mortality

atlan

Charles P. Craig, M.D. Sarah Connelly, B.S. Tampa,

Florida

Infection is a common complication in patients in hospital intensive care units (ICUs). Helms’ referred to the role of hygienic practice in the prevention of infections in ICUs. Findlay* described the role of patient isolation in control of such contagion in ICUs, alluding to the role of respiratory infection in outcome of ICU care. A factor in such infections was alleged to be the of gram-negative bacteria for “predilection” lungs of seriously ill patients and respiratory therapy equipment. Stevens et al.3 reported that 50% of patients who acquired pneumonia in ICUs died, suggesting that ICU-acquired pneumonia is the most lethal of all nosocomial infections. Despite claims to the contrary by LaForce,4 it is assumed that careful identification and control of risk factors could lessen both morbidity and mortality of ICU-acquired pneumonia in adults. C. Baker (personal communications) has identified the risk factors for nosocomial pneumonia in neonates as the following: crowding, nurse/patient ratio, prior antibiotic treatment, duration of hospitalization, contaminated life-support equipment, and prematurity (as well as other host factors). However, little information is available concerning risk factors for nosocomial pneumonia acquired by adults in ICUs and the impact of these infections on duration of hospitalization and mortality. This study demonstrates that pneumonia is From the University of South Florida College James A Haley Veterans Hospital, Tampa Area tion Control Program.

of Medicine, Hospital Infec-

Reprint requests: Charles P. Craig, M.D., Professor cine, Director, Division of Infectious and Tropical USF College of Medicine, Box 19, 12901 North Tampa, FL 33612.

of MediDiseases, 30th St.,

the most common nosocomial infection among ICU patients, that it significantly prolongs the stay of patients in ICUs, and that it significantly increases mortality. Data on all patients were collected prospectively and then analyzed, employing the technique of case matching of patients with pneumonia to demographically similar patients without pneumonia. MBTHOOB Patients admitted to the ICUs of six community hospitals between April 1978 and July 1979 were eligible for surveillance. Because of the difference in size of these units, some had all patients prospectively evaluated, whereas other units with more than 14 beds had every fourth or fifth patient randomly selected for study with the use of a table of random numbers. Demographic and clinical data collected included date of admission, age, sex, hospital, presence of infection on admission, general host factors such as acidosis, alcoholism, chronic organ failure, malignancy, malnutrition, shock, steroid or antibiotic therapy, and reason for admission. Use of respiratory therapy equipment, nasogastric or urinary drainage tubes, hemodialysis, and parenteral hyperalimentation was also recorded. All data were collected by experienced nurse epidemiologists who were supervised by the senior author (C.P.C.). Pneumonla. Episodes of pneumonia were classified as non-ICU-acquired pneumonia (NIP) and nosocomial ICU pneumonia (IP). Pneumonia was defined as oral temperature over 100.5” F at least once on 2 or more consecutive days, a new pulmonary infiltrate on x-ray examination not otherwise explained, purulent sputum, and presence of a significant respiratory pathogenic 233

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Craig and Connelly

T&le

1. Characteristics

American INFECTION

of study and control

Character&tics Age

Sex Male Female Admission diagnosis* Head trauma Other trauma Acute hemorrhage Thoracic surgery Peripheral vascular surgery Abdominal surgery Neurosurgery CVA Coma Acute Ml/heart failure Acute resp. failure Ethanolism Diabetic ketosis Chronic renal failure Chronic liver disease Mean No. of existing host factorst

patients

IP 56.3

Journal oi CONTROL

IPcontrols yr

57.2

35

35

19

19

9 10

9 9

5 6 2 2

3 5 0 4

yr

NIP 53.2 24

9

NIP controls yr

54.5 24 9

1

2

3 3 1 0 0

5 3 3 0 0

0

1

0

0

2

1

2

2

1 10

1

:

6 23

3 26

4 22

1 0

0 0

0 0

0 1

2 2 3.5

2 1 2.6

3 0 3.8

2 0 2.6

22

1

yr

*Totals exceed numbers of subjects because many patients had more than one major admission diagnosis. TUnderlying host factors present on admission to ICU but not constituting admission diagnoses: acidosis, alcoholism, chronic lung disease, chronic renal disease, collagen vascular disease, coma, diabetes, heart failure, leukemia/lymphoma. other malignancy, leukopenia. leukocytosis, malnutrition. obesity, peripheral vascular disease, severe liver disease, shock, steroid therapy, transfusion, and broad-spectrum antibiotics.

bacterium as the predominant organism on culture, or written doctor’s diagnosis of pneumonia. The criterion of a written doctor’s diagnosis was reviewed in every applicable case by the senior author (C.P.C.). Duration of stay. Date of discharge from the ICU or death was recorded. Total days in an ICU were calculated, counting first and last days as full days. For purposes of assessing the effect of pneumonia on length of ICU stay, patients who died in the ICU were omitted in these calculations because the multiple causes of death reflected the effect of all underlying diseases rather than the effect of pneumonia on duration of stay. Control patients. Patients without pneumonia were categorized by hospital and analyzed for uniformity by age, underlying disease, risk factors, duration of ICU stay, and mortality. Decause no differences were found among these categorized patients, all were considered together in the selection of case controls. Selection of controls. Data from all infected and uninfected patients were recorded on computergenerated data sheets, using numerical desig-

nations. Patients admitted to the ICU with pneumonia were arbitrarily categorized as having NIP. Those acquiring pneumonia in the ICU were classified as having IP. Controls for both groups were selected by the following criteria: ( 1) within 2 years of the age of the patients with pneumonia, (2) free of detectable or diagnosed pneumonia, (3) the same sex as the matched pneumonia patients, (4) had at least one of the same diagnoses on admission as their matched pneumonia patients, (5) had at least one existing host factor matching that of the corresponding pneumonia patient, and (6) were matched with pneumonia patients for the presence or absence of a surgical procedure. Characteristics of study and control patients are recorded in Table 1. The numerical distribution of admission diagnoses showed remarkable similarity between study groups and their controls. In general, pneumonia patients had a larger number of underlying host factors than their matched controls. IP patients and their controls both had a higher number of surgical procedures than NIP and NIP ccmtrols . Patients were followed up for 3 days after discharge

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Effect of ICU nosocomial

Table 2. Organisms with pneumonia

cultured

Table 3. Outcome of ICU care of patients “community” pneumonia

from patients

No. of patlents ICUacquired pneumonia

Organism

No culture No growth Gram-positive

14 0

1 1 1 7

0 0 1 3

pneumoniae agalactiae

Staphylococcus

epidermidis

0

10

Group

Average stay of survrvors (Days 2 2 SD)

Pneumonia Control

a.0 k 6.Y 4.2 -c 4

*Differs

Subtotal tuberculosis

“Normal” flora Mixed flora Multiple episodes

6 a

from control;

KU-acquired

5

11

1

3

0

11 1

1 0

ia

5

1

0

3

3

1

0

63 0 5 16 5

15 2 4 3

from the ICU and then were dropped from the study. This was done because change in location, intensity of care, and treatment factors associated with transfer from the ICU introduced new risk factors that would dilute the quality of observation based on ICU care. RESULTS Data on 670 patients were collected. Analyses were performed with the paired data via student’s t test.5 The incidence rate of nosocomial infection by site was respiratory tract 8.8%, urinary tract 7.7%, wound 3.1%, sepsis (primary and secondary) 2.8%, and other 4.0%. Twentysix percent of ICU patients had at least one nosocomial ICU infection. Four patients with ICUacquired pneumonia were excluded because of inadequate data. A total of 33 patients were admitted to the ICU with NIP, 54 with IP were recorded. The bacteria isolated from sputum or tra-

Group

Pneumonia Control *Differs tDiffers

from control; from control;

with

13133 (39%) 6/33

(18%)

= 3.62.

Average stay of survivors (Days f. 2 SD)

12.0 I! 7.5 4.3 f 3.3 chi square chi square

235

Mortality

of ICU care of patients pneumonia

1 0 5

chi square

Table 4. Outcome

rods

Escherichia co/i Klebsiella sp. Proteus mirabilis Other Proteus sp. Enterobacter sp. Cifrobacter sp. Pseudomonas aeruginosa Other Pseudomonas Serratia sp. Hemophilus influenzae Mycobacterium

Non-ICUacquired pneumonia

22 2

Other streptococci Staphylococcus aureus Subtotal Gram-negative

with

cocci

Streptococcus Streptococcus

pneumonia

with

Mortality

1 l/54 (20.3%)? 3/54(5.6%)

= 4.01. = 29.3.5

cheal secretions of patients with NIP or IP are listed in Table 2. The results show how often the sputum cultures grew a mixture of organisms and also demonstrate that cultures are not done for almost 40% of patients who acquire pneumonia in the study hospitals. In addition, the recognized predominance of gram-negative enteric bacteria, Staphylococcus aureus, and Pseudomonas is demonstrated. The culture results from patients with NIP are influenced by the fact that many of these episodes were indeed hospital acquired but originated outside the ICU. Thus 15 of these yielded gram-negative bacilli. It is interesting that Mycobacterium tuberculosis was isolated from two patients. This is a reflection of the relatively high rate of active tuberculosis in patients in the Tampa Bay area. The outcome of patients with NIP is presented in Table 3. Although 13 of 33 NIP patients and 6 of 33 controls died, the mortality was not different by statistical analysis. Average stay of 33 NIP patients was 8 days (range 1.5 to 14.5 days). Control patients had a stay only half as long, 4.2 days (range 1 to 8.2 days). The difference in stay comparing paired values with the use of student’s t test, was statistically significant (p = 0.01). Thus NIP did not appre-

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Craig and Connelly

Table 5. Prior use of respirator of hospital-acquired pneumonia

as determinant (HAP) On reepiretor

HAP

Yes’

No

Yes

36 19

18 35

No *Differ from no respirator;

chi square

= 25.3.$

ciably alter mortality, but it necessitated longer ICU stays. IP had a profound impact on mortality (Table 4). Deaths were nearly four times as common among patients with IP as among case controls. Among 43 survivors, the mean ICU stay was almost three times as long as that of corresponding case controls (12.0 vs. 4.3 days). The average stay of survivors was significantly greater than that of their matched case controls. A comparison among pairs with the use of student’s t test indicated a difference with a probability of error of less than 0.001. Severity of underlying disease was assessed to determine whether the greater impact of IP on ICU stay and mortality was due to more severe primary illness. The mortality of NIP controls was 18.2%; that for IP controls 5.5%. Since the major difference between the pneumonia patients and their respective controls was only the presence of pneumonia, it would appear that the same assessment of severity of underlying disease could be applied to both. As a measure of severity of underlying respiratory disease, the need for ventilator support was determined. Sixty-one percent of NIP controls required ventilator support; only 42% of IP controls did. Thus in evaluating the severity of underlying respiratory disease and mortality, there seems to be no suggestion that the IP group was more seriously ill than the NIP group. Two of the 33 patients admitted to ICUs with NIP had significant changes in the bacterial flora of their respiratory tracts during ICU care. In both cases this was associated with an extension of x-ray infiltrates. One of the two patients died. Both are included in the NIP group in this study because of the presence of pneumonia at the time of admission to the ICUs.

Journai

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CONTROL

Use of respirators prior to onset of clinical pneumonia was assessed in IP patients (Table 5). Patients who subsequently developed IP had prior respirator support twice as often as case controls. Duration of stay in the ICU, however, seemed to play no detectable role in causation of IP. Controls stayed in the ICU for a mean number of days precisely equal to the mean interval between admission and onset of IP in infected patients (4 days). Thus control patients had ample time to develop IP yet did not. COHCLU64OM6

Respiratory infections constituted the most frequent nosocomial infections among our ICU patients (29%). Such infections prolonged ICU stays threefold, adding significantly to the dollar cost of hospitalization. More important, mortality was nearly quadrupled by nosocomial pneumonia in ICU patients compared to control patients, even among those who were not among the most seriously ill on admission. The risk of acquiring pneumonia was linked to respiratory failure requiring use of mechanical ventilators. Respiratory failure alone was not associated with a higher mortality rate. Acute respiratory failure occurred with almost equal frequency in all groups (22 patients with IP, 23 IP controls, 26 with NIP, and 22 NIP controls). Moreover, pneumonia was not consequent to longer stay in an ICU. Others have reported that ventilatory support does not increase mortality.” Our results, drawn from only 13 patients, support that conclusion. Of 54 patients with nosocomial pneumonia, 35 were on ventilators and 19 were not. Of those intubated, 8 (23%) died; of those not intubated, 3 ( 16%) died. Thus, although respirator support was a risk factor for pneumonia and pneumonia led to higher mortality rates in ICU patients, other factors independent of respirator support were equally important determinants of death in patients with IP. Among the 60% of patients cultured, deaths related to Psetldomonas (7 of 18) were more frequent than among all patients with IP (39% vs. 20%), and Pseudomonas may have been the other factor increasing mortality. Flick and Cluff7 observed that when Pseudomonas pneumonia was further complicated

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by septicemia, mortality was 91%. Graybill et al.s observed a 54% mortality with Pseudomonas pneumonia. Our results differ from those of an earlier study. Stevens et a1.,3 in the late 1970s found that 50% of patients in a Boston hospital who acquired nosocomial pneumonia died. Only 20% of our subjects died. These differences may be due to improved treatment, although our own recent studies showed the newest broadspectrum treatment of ICU pneumonia (moxalactam) was no more successful than a combination of older antibiotics (ticarcillin plus cefazolin) (Craig, CP: Personal observations). Whether mechanical or other adjunctive treatment made the difference is unknown. Our techniques for identification of ICU-acquired pneumonia may have been more sensitive, thus leading to the inclusion of patients with milder disease, but careful review of the article by Stevens et al. does not suggest this. Nonetheless, as emphasized by Gross et a1.g pneumonia is involved in 60% of deaths from nosocomial infection. Our bacteriologic data show the reluctance of many clinicians in our hospitals to obtain cultures from patients with pneumonia. Thirty-six of our 87 patients with clinical diagnoses of pneumonia did not have cultures performed. Controversy about the value of cultures of orally collected sputum in pneumonia’, lo-l5 accounts for a majority of the episodes of pneumonia without cultures in our series. However, in the ICU it certainly should be possible to collect tracheal secretions to assist in the selection of proper therapy for these challenging infections. The high mortality rates among our patients as well as those in other studies and the wide range of bacterial pathogens isolated from those with cultures indicated a need for individualization based on culture results. Our data also shows the important role played by gram-negative bacilli in the etiology of pneumonia in seriously ill patients. Not only those who acquired infections in the ICU but those admitted from other hospital settings or from the community at large had a preponderance of gram-negative bacilli as assumed etiologic agents in pneumonia. Also no-

Effect of ICU nosocomial pneumonia

237

table was the frequency of Pseudomonas isolated from multiple extrapulmonary sites in patients with Pseudomonas pneumonia. The most common of these sites was the urinary tract. Five of the 18 patients with Pseudomonas were found to have extrapulmonary Pseudomonas infections, One had Pseudomonas wound infection followed several days later by Pseudomonas pneumonia; two others had antecedent Pseudomonas urinary tract infections. It was instructive to observe that 28% of the patients with KU-acquired pneumonia had a mixture of organisms on culture. For purposes of epidemiology as well as patient management, careful collection of sputum specimens from these patients is essential. With good specimen collection, it is the rule rather than the exception that single pathogens predominate. The observation that 65% of patients with ICU-acquired pneumonia and 73% of those with community-acquired pneumonia were males was interesting. The recognized preponderance of lung cancer, chronic obstructive pulmonary disease, and pneumonia in males is curious.lG The three findings may be unrelated. Nonetheless, it is well established that exposure of males to inhaled pollutants in industrial and agricultural settings, and in cigarette smoke is associated with the higher rate of pulmonary diseases in men in the United States. It is likewise clear that severity of pulmonary infection and consequences of pneumonia are greater in those with underlying lung disease, including chronic obstructive pulmonary disease or a history of smoking, than in those without. These or yet undiscovered risk factors may have influenced our results. We acknowledge the invaluable contributions of the following practitioners of the Tampa Area Hospital Infection Control Program: Julia Cancela, R.N., Dolores 0. Craig, B.S.N., Lucille Emberton, B.A., R.N., Catherine Farese, B.S., R.N., Dorothy Lieson, M.S., R.N., Catherine Ricchezza, R.N., Mary Robinson, R.N., B.S.N., Joan Sargent, R.N., B.S., and Dianne Yates, R.N. We also acknowledge the assistance of Mrs. Edwina Lucco for manuscript typing.

References 1. Helms P: Hygiene in an intensive care unit . Acta Anesthesiol Stand 23:(Suppl) 103- 107, 1966.

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2. Findlay SW Jr: Sepsis in the surgical intensive care unit. Med Clin North Am 55: 1331- 1352, 197 1. 3. Stevens RM, Teres D, Skillman JJ, Feingold DJ: Pneumonia in an intensive care unit. Arch Int Med 134: 106-111, 1974. 4. LaForce FM: Hospital-acquired gram-negative rod pneumonias. An overview. Am J Med 70:664-669, 198 1. 5. Sokal RR, Rohlf FJ: Introduction to biostatistics. San Francisco, 1973, W. H. Freeman & Co., pp. 107 ff, 288, 290. 6. Zwillich CW, Pierson DJ, Creagh CE, Sutton FD, Schatz E, Petty TL: Complications of assisted ventilation. A prospective study of 534 consecutive episodes. Am J Med 57: 161- 170, 1974. 7. Fhck MR, Cluff LE: Pseudomonas bacteremia. Am J Med 60:501-508, 1976. 8. Graybill JR, Marshall LW, Charache P, Wallace CK, Melvin VB: Nosocomial pneumonia. Am Rev Resp Dis lOs:1130-1140, 1973. 9. Gross PA, Neu HC, Aswapokee P, Antwerpen C, Aswapokee N: Deaths from nosocomial infections. Experience in a university and community hospital. Am J Med 68:219-223, 1980.

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10. Mostow SR: Diagnosis and treatment of bacterial pneumonia. Hosp Med 11:36-56, 1975. 11. Flataker RE, Chabalko JJ, Wolinsky E: Fiberoptic bronchoscopy in bacteriologic assessment of lower respiratory tract secretions. JAMA 244:2427-2429, 1980. 12. Gerding DN: Etiologic diagnosis of acute pneumonia in adults. Postgrad Med 60: 136- 150, 198 1. 13. Haas H, Morris JF, Samson S, Kilbourn JP, Kim PJ: Bacterial flora of the respiratory tract in chronic bronchitis: Comparison of transtracheal, fiberbronchoscopic, and oropharyngeal sampling methods. Am Rev Resp Dis 116:41-47, 1977. 14. Rein MF, Gwaltney JM, O’Brien WM, Jennings RH, Mandell GL: Accuracy of Gram’s stain in identifying pneumococci in sputum. JAMA 239:2671-2673, 1978. 15. Thorsteinsson SB, Musher DM, Fagan T: The diagnostic value of sputum culture in acute pneumonia. JAMA 223:894-895, 1975. 16. Wyngarden JB, Smith LH Jr, editors: Cecil textbook of medicine, ed 16. Philadelphia, 1982, W.B. Saunders Co., pp. 367, 414.

The Twelfth Annual APIC Educational Conference will be held in Cincinnati, Ohio, May 12-16, 1985. The National Program Committee will again solicit abstracts of papers to be presented. As in past years, authors may request either oral presentation or poster format. The “Call for Abstracts” and the official abstract form will be published in the October 1984 issue of the American Journal of Infection Control. Guidelines for the presentation of an acceptable abstract will also appear in that issue.