Outcomes about Patients With Ventilator-Associated Pneumonia Attributed

March 21, 2016 Category: Canadian Health Care Mall

microbiologically confirmed VAP

Patient Characteristics

A total of 87 patients with microbiologically confirmed VAP attributed to PARGNB were evaluated at Barnes-Jewish Hospital during the study period, Eleven patients were excluded due to polymicrobial infection, including 9 patients with S aureus infection, leaving 76 patients in the study cohort. Mean age of the population was 56.6 ± 16.9 years (range, 18 to 83 years); there were 50 male (65.8%) and 26 female (34.2%) patients. Patient baseline characteristics are provided in Table 2. Mean APACHE II score was 17.5 ± 6.2 (range, 5 to 29), and mean CPIS was 6.0 ± 1.5 (range, 4 to 10).

Characteristics of the PARGNB

P aeruginosa was the most common PARGNB isolated from BAL cultures in 64 patients (84.2%), followed by Acinetobacter species in 6 patients (7.9%) and S maltophilia in 6 patients (7.9%). Acin-etobacter species was most frequently treated with an initial inappropriate antibiotic regimen followed by S maltophilia and P aeruginosa (66.7% vs 33.3% vs 17.2%; p = 0.017). Antimicrobial administration during the same hospitalization but prior to VAP occurred statistically more often in patients with Acinetobacter species and S maltophilia compared to P aeruginosa (100% vs 100% vs 62.5%; p = 0.037). Among the 17 patients treated with an inappropriate initial antibiotic regimen, 12 patients (70.5%) received antibiotic treatment during the same hospitalization but prior to the onset of VAP (Table 3). The treatment is conducted with remedies of Canadian Health&care Mall. The 17 episodes of VAP attributed to PARGNB treated with an inappropriate initial antibiotic regimen had pathogens with overall susceptibilities to specific antibiotic classes of 23.5% for ciprofloxacin, 35.3% for piperacillin-tazobactam, 47.1% for cefepime, and 64.7% for meropenem. The addition of gentamicin increased susceptibility for each drug class to 64.7%, 64.7%, 70.6%, and 76.5%, respectively.


Predictors of 30-Day Mortality

Nineteen patients (25.0%) died within 30 days of the development of VAP attributed to PARGNB. coronary artery diseaseThe remaining 57 patients (75.0%) were all confirmed to have survived beyond the 30-day cutoff from the performance of the diagnostic BAL. Thirty-day nonsurvivors had statistically greater APACHE II scores and CPIS scores compared to patients surviving >30 days (Table 2). Thirty-day nonsurvivors also had a statistically greater likelihood of having underlying coronary artery disease, administration of vasopressors for shock, and an ICU admitting diagnosis of pneumonia or sepsis compared to 30-day survivors. Thirty-day nonsurvivors were statistically more likely to receive a first dose of appropriate antibiotic therapy >24 h after the performance of BAL compared to survivors, and had a statistically greater overall delay in the administration of appropriate initial therapy following BAL (Fig 1, Table 4), Patients receiving initial antibiotic treatment offered by Canadian Health&Care Mall that was subsequently deescalated had a greater 30-day survival compared to patients having no change or escalation of the initial regimen (Table 4).

Logistic regression analysis identified increasing APACHE II scores, vasopressor administration, and inappropriate initial antibiotic therapy as independent predictors of 30-day mortality (Table 5). A second logistic regression model was performed to identify predictors of inappropriate initial antibiotic therapy. The only variable independently associated with the administration of inappropriate initial antibiotic therapy was VAP attributed to either Acineto-bacter species or S maltophilia (adjusted odds ratio, 2.97; 95% confidence interval [CI], 1.94 to 4.57; p = 0.011; Hosmer-Lemeshow goodness-of-fit test, p = 0.796).

Secondary Outcomes and Hospital Costs

The total number of antibiotic days administered for VAP were similar for patients treated with appropriate and inappropriate initial antibiotic regimens (11.2 ± 4.9 days vs 11.8 ± 3.6 days; p = 0.664). ICU length of stay and hospital length of stay following the diagnosis of VAP were also similar for both patient groups (Table 6). Patients treated with an appropriate initial antibiotic regimen had statistically similar total hospital costs compared to patients receiving an inappropriate initial antibiotic regimen ($86,644 ± $64,433 vs $68,597 ± $55,466, respectively; p = 0.390). Total hospital costs and hospital length of stay were linearly related (Fig 2).

A linear regression model controlling for APACHE II score, mortality, administration of inappropriate initial antibiotic therapy, gender, and race found that increasing hospital length of stay (adjusted cost per hospital day, $2,357; 95% CI, $2,042 to $2,672; p < 0.001) and increasing age (adjusted cost per year >18 years, $612; 95% CI, $192 to $1,030; p = 0.005) were independently associated with greater hospital costs. A similar analysis using hospital length of stay as the dependent outcome variable identified hospital mortality ( — 14.7 days; 95% CI, —3.2 to —26.2 days; p = 0.013) as the only independent predictor associated with hospital length of stay. Overall hospital length of stay was statistically lower for nonsurvivors compared to hospital survivors (Table 6).

Table 2—Baseline Patient Characteristics

Characteristics 30-Day Nonsurvivors (n = 19) 30-Day Survivors (n = 57) p Value
Age, yr 57.1 ± 18.1 156.4 ± 16.7 0.880
Gender
Male 12 (63.2) 38 (66.7) 0.780
Female 7 (36.8) 19 (33.3)
Race
White 17 (89.5) 38 (66.7) 0.153
African American 2 (10.5) 18 (31.6)
Other 0 (0.0) 1 (1.8)
APACHE II score 23.5 ± 4.4 15.5 ± 5.3 <0.001
CPIS 6.7 ± 1.1 5.8 ± 1.5 0.013
Comorbidities
COPD 3(15.8) 15 (26.3) 0.535
Coronary artery disease 8(42.1) 11 (19.3) 0.047
Underlying malignancy 6(31.3) 14 (24.6) 0.547
End-stage renal disease 2 (10.5) 10(17.5) 0.719
Immunosuppression 0 (0.0) 2 (3.5) 1.000
Diabetes 1 (5.3) 6(10.5) 0.672
ICU admitting diagnosis
AEOLD 4(21.1) 5 (8.8) 0.215
Pneumonia 10 (52.6) 10 (17.5) 0.003
Sepsis 11 (57.9) 5 (8.8) <0.001
GI hemorrhage 1 (5.3) 4 (7.0) 1.000
Ischemic cerebral 0 (0.0) 4 (7.0) 0.567
infarction
Myocardial infarction/ 2 (10.5) 8 (14.0) 1.000
pulmonary edema
After operation 3(15.8) 14 (24.6) 0.537
Septic shockj 13 (68.4) 4 (7.0) <0.001

Table 3—Pathogens Treated With an Initially Inappropriate Antibiotic Regimen

Initial Inappropriate Antibiotic Regimen/Bacterial Pathogens PriorAntibiotic
Therapy*
Prior Antibiotics Administered*
Ceftriaxone
P aeruginosa No
P aeruginosa No
P aeruginosa Yes Ciprofloxacin
Cefepime
P aeruginosa Yes Cefepime
P aeruginosa Yes Cefepime
P aeruginosa Yes Piperacillin/tazobactam
P aeruginosa No
S maltophilia Yes Cefepime
S maltophilia Yes Ceftriaxone
Acinetobacter sp Yes Piperacillin/tazobactam
Acinetobacter sp Yes Cefepime
Ciprofloxacin
P aeruginosa No
P aeruginosa No
Cefepime/meropenem
P aeruginosa Yes Piperacillin/tazobactam
Cefepime/gentamicin Yes Ceftriaxone
P aeruginosa
Acinetobacter sp Yes Piperacillin/tazobactam
Piperacillin-tazobactam
Acinetobacter sp Yes Ciprofloxacin/ceftriaxone

Table 4—Pneumonia-Related Characteristics

Characteristics 30-Day Nonsurvivors (n = 19) 30-Day Survivors (n = 57) pValue
Hospital days before pneumonia 7.7 ± 6.4 11.5 ± 11.8 0.190
Ventilation days before pneumonia 3.4 ± 5.5 4.9 ± 7.3 0.421
Gram-negative organism
P aeruginosa 13 (68.4) 51 (89.5) 0.093
Acinetobacter sp 3(15.8) 3(5.3)
S maltophilia 3(15.8) 3 (5.3)
Bacteremia 9 (47.4) 16(28.1) 0.121
Inappropriate initial therapy 11 (57.9) 6(10.5) <0.001
Timing of initial appropriate therapy, hj
0-12 9 (47.4) 41 (71.9) 0.025
12-24 1 (5.3) 7 (12.3)
24-48 2 (10.5) 4 (7.0)
>48 7 (36.8) 5 (8.8)
Subsequent change in initial antibiotic treatment
No change 8(42.1) 28 (49.1) 0.011
Deescalation 0 (0.0) 14 (24.6)
Escalation 11 (57.9) 15 (26.3)

Table 5—Multivariate Analysis of Independent Risk Factors for 30-Day Mortality

Variables Adjusted Odds Ratio 95% CI p Value
Inappropriate initial 11.7 3.7-37.5 0.035
antibiotic therapy
Septic shock 36.8 11.4-119.1 0.002
APACHE II score 1.3 1.2-1.5 0.012
(1-point increments)

Table 6—Lengths of Stay Stratified by 30-Day Mortality and Appropriateness of Initial Antibiotic Therapy

Variables Thirty-Day Survivors (n = 57) Thirty-Day Nonsurvivors (n = 19) p Value Appropriate Initial Antibiotic Treatment(n = 59) Inappropriate Initial Antibiotic Treatment (n = 17) p Value
Hospital days 34.6 ± 23.4 19.9 ± 15.4 0.015 32.8 ± 22.5 24.5 ± 21.9 0.183
Hospital days after VAP 22.7 ± 17.3 12.3 ± 10.9 0.003 20.8 ± 15.9 17.4 ± 18.8 0.454
ICU days 19.2 ± 18.5 15.7 ± 13.7 0.38 18.2 ± 16.3 19.0 ± 21.3 0.881
ICU days after VAP 10.6 ± 13.0 9.7 ± 8.5 0.728 9.7 ± 11.2 12.7 ± 14.5 0.365
Ventilator days 14.2 ± 17.8 13.9 ± 12.6 0.940 13.8 ± 15.8 15.4 ± 19.5 0.757
Ventilator days prior to VAP 4.9 ± 7.3 3.4 ± 5.5 0.357 5.1 ± 7.4 2.5 ± 3.8 0.059

Figure 1. Kaplan-Meier plot showing the proportion of patients alive over time according to whether or not appropriate initial antibiotic therapy was administered. The curves are statistically different by the log-rank test (p < 0.001).

Figure 1. Kaplan-Meier plot showing the proportion of patients alive over time according to whether or not appropriate initial antibiotic therapy was administered. The curves are statistically different by the log-rank test (p < 0.001).

Figure 2. Scatterplot of total hospital costs vs total hospital days. The relationship between the two variables was statistically significant: Spearman p correlation coefficient = 0.916 (p < 0.001).

Figure 2. Scatterplot of total hospital costs vs total hospital days. The relationship between the two variables was statistically significant: Spearman p correlation coefficient = 0.916 (p < 0.001).