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Article
Vol. 14. No. 3
Eur. J. Clin. Microbiol. Infect. Dis., 1995, 14:176-181
Retrospective Analysis of Risk Factors and Prognosis in Non-Ventilated Patients with Nosocomial Pneumonia
J. G6mez 1., A. Esquinas 1, M.D. Agudo 1, J.M. S~inchez Nieto 2, M.L. Ntifiez 3, V. Bafios 1, M. Canteras 4, M. Valdes 5 Although nosocomial pneumonia in non-ventilated patients continues to be frequent and have high mortality rates, knowledge of the associated risk and prognostic factors is still limited. This retrospective study was designed to analyze epidemiological characteristics, risk and prognostic factors in patients with nosocomial pneumonia admitted to a hospital internal medicine department. Data on epidemiological, clinical and microbiological factors as well as diagnosis and clinical course were obtained from the medical records of 104 patients diagnosed with nosocomial pneumonia, according to Centers for Disease Control criteria, and from 104 control subjects. The incidence of nosocomial pneumonia was 18.8 per 1000 admissions. Risk factors significantly associated with contracting the disease were female sex, hospital stay longer than 14 days, other admission in the previous month and use of antibiotics during the previous six weeks. The most frequent underlying diseases were cardiorespiratory in nature (59.4 %). Prognostic factors significantly associated with increased mortality were serious underlying disease, initially critical clinical status, severe and moderate respiratory insufficiency and bilateral radiological signs. More epidemiological data are needed to improve the diagnosis, treatment and prevention of nosocomial pneumonia.
Nosocomial p n e u m o n i a continues to be a major medical problem, despite recent advances in prevention and treatment, It has the highest mortality rate (20 % - 5 0 % ) of all hospital infections (1) and currently has the third highest incidence (510 per 1000 admissions) of all hospital infections in Spain (2, 3), Surprisingly little information is available on this disease in non-ventilated patients (4, 5).
diagnostic features in these patients and to identify risk and prognostic factors which might help to prevent nosocomial p n e u m o n i a or to improve the m a n a g e m e n t of this disease.
This retrospective study analyzed a group of nonventilated patients with nosocomial pneumonia who were admitted to an internal medicine department of a large, tertiary facility. Our objectives were to define epidemiological, clinical and
Patients and Study Groups. The hospital records of 114 non-ventilated patients with nosocomial pneumonia admitted to the internal medicine department between July 1989 and July 1993 were reviewed. The diagnostic criteria for nosocomial pneumonia were those published by the Centers for Disease Control, Atlanta, USA (6). A patient's record was included in the study when it indicated: fever, dyspnea, cough and purulent expectoration, leukocytosis greater than 12,000/ram3 and radiological evidence of recently occurring, previously absent pulmonary infiltrate within 72 h of hospital admission; or the appearance of the same clinical signs at home, with the antecedent of a previous hospital admission during the previous month. To study risk factors, a control group of 104 randomly chosen
l Internal Medicine Service, Infectious Diseases Unit, 2Pneumology Section, and 3Microbiology Section, Virgen de Arrixaca University Hospital, Plaza de la Cruz Roja, 30003 Murcia, Spain. 4Department of Biostatistics, and 5Department of Medicine, School of Medicine, University of Murcia, 30100 Espinardo, Murcia, Spain.
Patients and M e t h o d s
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patients from among those admitted during the same period, with the same underlying disease but without nosocomiaI pneumonia was analyzed.
Epidemiological and Clinical Data. For all study and control patients, age, sex, type of underlying disease, initial clinical status, previous respiratory infections, use of steroids and antibiotics during the previous six weeks, hospital admission during the previous month and length of hospital stay were noted. The criteria of McCabe and Jackson (7) were used to classify the patients according to the prognosis of their underlying disease (rapidly fatal, eventually fatal or nonfatal), and the criteria of Winston (8) were used to classify their initial clinical status as critical, poor or fair. The degree of respirator), insufficiency was determined on the basis of the partial 02 pressure (pO2) as serious (below 50 mmHg), moderate (below 60 mmHg) or slight (60-70 mmHg). Radiological Studies of all patients included in the study and controls were evaluated by two independent observers, who classified the findings as unilateral or bilateral pulmonary infiltrate. Bronchoscopy with a telescope catheter was done in patients admitted to intensive care and in those who showed a poor response to treatment on the third or fifth day after admission.
Microbiological Studies. The etiological agent was noted only when the microorganism was isolated from blood cultures, pleural fluid, valid samples of bronchial secretions collected by bronchoscopy and telescope catheter or sputum containing more than 25 polymorphonuclear cells per field, fewer than eight squamous cells and a
positive Gram stain "(4). Occasionally, immunofluorescence studies for Legionella spp. were done in patients with refractory or progressive pneumonia. Serological tests for viruses or Chlamydia pneumoniae were not conducted.
Clinical Course and Treatment. Mortality and cure were noted; the latter was defined as the disappearance of signs, symptoms and radiological abnormalities and the finding of sterile blood cultures in patients whose infection was microbiologically documented. Antibiotic treatment was considered appropriate when the microorganism isolated as responsible for nosocomial pneumonia was sensitive to the antibiotic chosen or when treatment was in accordance with therapeutic protocols developed by our hospital's commission on infectious diseases and with our center's policy on antibiotic treatment (9, 10). Response to antibiotics was assessed on the basis of the patient's course during hospitalization and in subsequent followup examinations, in accordance with the criteria of the American Society of Microbiology (11). Death was attributed directly to nosocomial pneumonia when it occurred during the course of the disease and was considered unrelated to nosocomial pneumonia if it occurred after the disease was considered cured. Analysis of Risk Factors. As possible risk factors we noted the patient's sex, age, length of hospitalization, previous admissions, previous treatments with corticosteroids or antibiotics and type of underlying disease. Analysis of Prognostic Factors. We noted the patient's clinical course: cure or death, age, sex, previous admissions, previous infections, previous treatment with cor-
Table 1: Riskfactors associated with nosocomial pneumonia. Control group (n = 104)
Study group (n = 104)
Age < 65 years > 65 years
42 62
40 64
NS
Sex Male Female
76* 28
56 48*
0.01
Underlying disease Cardiopulmonary Other
60 44
66 38
NS
Duration ofhospitalstay 10 days 10--14 days >14days
72" 17 15
50 18 36*
0.01
Admitted in the previous month Yes No
20 84*
59* 45
0.001
Antibiotics in the previous 6 weeks Yes No
28 76*
42* 62
0.05
Previous corticosteroid treatment Yes No
23 81
30 74
NS
*Refers to p value. NS = not significant.
P value
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Eur. J. Clin. Microbiol. Infect. Dis.
ticosteroids or antibiotics, length of hospitalization, prognosis of underlying disease, initial clinical status, degree of respiratory insufficiency, radiological findings, whether causal microorganisms were isolated, serum albumin and type of antibiotic treatment.
Statistical Analyses. The findings in the two groups were compared using variable contingency tables, Pearson's test and Fisher's exact test.
Results
Incidence and Demographic Characteristics. Of the 5521 patients admitted to the internal medicine department of our hospital during the study period, 104 had nosocomial pneumonia, representing an incidence of 18.8 cases per 1000 admis-
Table 2: Prognostic factors in nosocomial pneumonia. Cure (n = ~3)
Death (n = 21 )
Age < 65 years > 65 years
33 50
7 14
NS
Sex M ale Female
43 40
13 8
NS
Underlying disease Cardioputmonary Other McCabe II McCabe 111
53 30 34 49*
13 8 18* 3
Duration of hospital stay 10 days 10-14 days > 14 days
40 14 29
10 4 7
NS
Admitted in the previous month Yes No
48 35
11 10
NS
Antibiotics in the previous 6 weeks Yes No
34 49
8 13
NS
Previous corticosteroid treatment Yes No
19 64*
11" 10
0,01
Initial clinical status Critical or poor Fair
41 42*
21" 0
0.001
Respiratory insufficiency Severe and moderate (pO2 < 60) Mild (pO2 60-70)
41 42*
21 * 0
0.001
Radiological changes Unilateral Bilateral
71 * 12
11 10*
0,001
Microorganisms isolated Yes No
20 63
2 19
NS
Type of treatment Monotherapy Combination
40 43
12 9
NS
Serum albumin <3g/l > 3 g/I
15 68
2 19
NS
*Refers to p value. NS = not significant.
P value
NS 0.001
Vol. 14, 1995
sions; More men than women had nosocomial pneumonia (76 versus 28), and the mean age of the affected patients was 58 + 14 years. None of the nosocomial pneumonia patients had a rapidly fatal underlying disease, and there were 52 patients with eventually fatal and 52 with nonfatal disease. The most frequent underlying diseases, found in 66 patients (63.4 %), were cardiorespiratory (chronic obstructive pulmonary disease and congestive heart failure) followed by neurological disease (9 cases), post-abdominal surgery complications (9 cases) and neoplasms (8 cases). The remaining 12 patients had other dis-
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significantly associated with increased mortality. No significant association was found between mortality and age, sex, other underlying diseases, hospitalization during the previous month, previous use of antibiotics, type of microorganism isolated, length of hospital stay, serum albumin concentration and type of antibiotic treatment (monotherapy or combination therapy) (Table 2).
Discussion
eases,
The initial clinical status was critical or poor in 62 patients. Previous respiratory infection and previous treatment with antibiotics were found in 42 patients, 30 of whom had received previous treatment with corticosteroids. Fifty patients stayed in the hospital for ten days, 18 for 11 to 14 days and 36 for more than 14 days. Severe or moderate respiratory insufficiency (pO2 below 60 mmHg) was present in 40 patients; eight of them required mechanical ventilation. Unilateral pulmonary infiltrate was seen in 82 patients. In microbiological studies organisms were isolated in samples from only 22 patients (5
Legionella, 7 Pseudornonas aeruginosa, 4 StreptoCOccus pneumoniae, 2 Klebsiella pneumoniae, 1 Escherichia coli, 1 Enterobacter cloacae and 2 Staphylococcus aureus). All the Legionella infections occurred in immunodepressed patients treated with corticosteroids. Antibiotic treatment Was considered appropriate for 102 of the patients. Nosocomial pneumonia was cured in 83 patients and was fatal in the remaining 21.
Risk Factors. Comparisons of nosocomial pneumonia patients with control patients who had similar underlying diseases without nosocomial pneumonia showed that female sex, hospital stays longer than 14 days, admission during the previous month and use of antibiotics during the previous six weeks were significantly associated with contracting nosocomial pneumonia. Age and use of corticosteroids during the previous six weeks Were not significantly associated with the appearance of nosocomial pneumonia (Table 1). Prognostic Factors. Nosocomial infection led to death in 20 % of the patients (n = 21) in our study and was cured in the remaining 80 % (n = 83). The previous use of corticosteroids, severe underying disease, initially critical clinical status and severe or moderate respiratory insufficiency were
The high incidence and mortality rates of nosocomial pneumonia among patients not on mechanical ventilation are of continuing concern (13). The 20 % mortality in the present sample of patients, although lower than the 36.6 % reported for another Spanish study (4), is similar to the rate found in a recent American study (5). The differences are probably due to the type of facility, type of medical department caring for the patients, patient characteristics and type of nosocomial pneumonia, higher mortality rates being associated with microorganisms such as Pseudomonas aeruginosa, Enterobacter spp. and polymicrobial flora. The scarcity of microbiological data on our patients meant that we could not adequately assess etiological features in this retrospective study. The microbiological agent responsible for nosocomial pneumonia could be documented in only 22 patients; in this regard, our study differs markedly from prospective research, which has shown that the microbiological agent can be documented in 40 to 60 % of the patients when invasive diagnostic procedures such as bronchoalveolar lavage, telescope bronchoscopy or fine-needle percutaneous pulmonary puncture are used systematically (5,12,13). In contrast with an earlier study that noted malnutrition, neurological disease and tracheal intubation as the major risk factors for nosocomial pneumonia (14), we found female sex, hospital stays longer than 14 days, hospital admission during the previous month and use of antibiotics during the previous six weeks to be most frequently associated with contraction of nosocomiat pneumonia. These discrepancies may be due to the different study designs (retrospective versus prospective), differences in the populations studied or differences in the mean ages of the groups of patients. With regard to age, Harkhess et al. (15) showed that in elderly patients, difficulty in expelling oropharyngeal secretions and
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the presence of a gastric tube were the greatest risk factors. The five patients in our study with nosocomial pneumonia caused by Legionella pneumophila had previously been treated with corticosteroids. This agrees with another study, which showed an apparent relationship between corticosteroid treatment and this type of nosocomial pneumonia (16). Our findings for prognostic factors were similar to those in other studies (4, 5). Serious underlying disease, critical clinical status, severe or moderate respiratory insufficiency, pO2 below 60 mmHg and radiological findings of bilateral lung infiltrate were significantly associated with increased mortality. However, unlike other authors (17), we found no prognostic association between mortality and age, possibly because of the different relative frequencies of underlying diseases. In our study, the most frequent underlying diseases were cardiorespiratory diseases. Differences in the medical departments caring for nosocomial pneumonia patients may also have accounted for part of this discrepancy, as we included only patients admitted to the internal medicine department, whereas an earlier study investigated medical, surgical and intensive care patients (4). Although we could accurately assess the suitability of antibiotic treatment only in those patients in whom the microorganism responsible for nosocomial pneumonia had been identified, we found only two cases in which the treatment was judged inappropriate. Like other authors, we found no significant differences in outcome between appropriate treatments with different types of medication, including monotherapy with third-generation cephalosporins, imipenem or ciprofloxacin or combination therapy with beta-lactams (piperacillin or ceftazidime plus amikacin) (18-22). However, because of the negative influence of inappropriate treatment on prognosis (23), new, noninvasive and invasive diagnostic methods should be implemented to improve the chances that medication will be effective in these patients ( 2 4 2 6 and J. Carratala et at., 31st ICAAC, Chicago, 1991, Abstract no. 994). We conclude that an understanding of risk and prognostic factors facilitates the choice of effective antibiotic therapy, improves the patient's clinical course and helps prevent nosocomial pneumonia.
Acknowledgement We thank Ms. Karen Shashok for translating the original manuscript into English.
Eur. J. Clin. Microbiol. Infect. Dis.
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