Outlet of Incidence, Etiology, Timing, and Risk Factors for Clinical Failure in Hospitalized Patients With Community-Acquired Pneumonia

Clinical Failure

Incidence of Clinical Failure

From a total of 500 consecutive patients with CAP who were enrolled during the study period, 67 patients (13%) met at least one of the three criteria for clinical failure. The clinical failure criteria for acute pulmonary deterioration were fulfilled in 39 patients (8%), those for acute hemodynamic deterioration were fulfilled in 10 patients (2%), and those for in-hospital death were fulfilled in 36 patients (7%). Some patients met more than one criterion on the day that clinical failure was diagnosed.

Etiology of Clinical Failure

A definite etiology of clinical failure was established by an agreement of the review committee in 63 of 67 patients (94%). Not enough clinical data were available for the review committee to characterize the etiology of clinical failure in four patients. Clinical failure was defined as being related to CAP in 54 of 67 patients (81%) and as being unrelated to CAP in 9 of 67 patients (13%). The rate of clinical failure related to CAP in the study population was 11% (54 of 500 patients). Table 1 shows the etiology of clinical failure related to CAP and unrelated to CAP. Among the patients whose clinical failure was related to CAP, one patient had a combined etiology. Among all patients who experienced clinical failure due to severe sepsis, four experienced clinical failure due to septic shock overcome with Canadian Health&Care Mall.

Timing of Clinical Failure

The mean time to clinical failure found in the study population was 3.7 ± 3.4 days (range, 0 to 18 days). Clinical failure related to CAP occurred significantly earlier in comparison to clinical failure unrelated to CAP (3.0 ± 2.6 vs 6.2 ± 4.9 days, respectively; p = 0.002). The distribution of CAP related time to clinical failure is shown in Figure 1, Fifty percent of clinical failures due to severe sepsis occurred on the first day of hospitalization (9 of 18 patients) and > 90% occurred in the first 72 h (17 of 18 patients). No significant pattern was identified in patients for the time to clinical failure unrelated to CAP (day 0, one patient; day 3, two patients; day 4, three patients; day 7, one patient; day 12, one patient; day 18, one patient).

Factors Associated With Clinical Failure Related to CAP

Tables 2, 3 show demographics; severity of disease; clinical, laboratory, and radiologic findings; treatment data; and clinical outcomes with significant univariate association with clinical failure related to CAP. The multivariable logistic regression model showed that advanced age (p = 0.027), a positive history for congestive heart failure (p = 0.022), hypotension (p = 0.001), alteration of gas exchange (p = 0.005), acidemia (p = 0.001), hypothermia (p = 0.019), the presence of pleural effusion (p = 0.005), and thrombocytopenia (p = 0.002) on hospital admission were independent predictors of clinical failure related to CAP (Fig 2).

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Table 1—Etiology of Overall Clinical Failure

Etiologies Patients, No. (%)
Clinical failure related to CAP (n = 54)
Severe sepsis 18 (33)
Acute myocardial infarction 15 (28)
Progressive pneumonia 10(19)
Exacerbation of CHF 5(9)
Cardiac arrhythmia 2(4)
Endocarditis 1(2)
Empyema 1 (2)
AECB 1 (2)
Pulmonary embolism 1 (2)
Mucus plug 1 (2)
Clinical failure unrelated to CAP (n = 9)
Hospital-acquired pneumonia 4 (45)
Iatrogenic pneumothorax due to CVC 1 (11)
Benzodiazepine overdose-induced ARF 1 (11)
GI bleeding 1 (11)
Aspiration of gastric content 1 (11)
Iatrogenic bleeding in pleural space 1 (11)

Table 2—Demographics, Comorbidities, Severity of Disease, and Physical Findings According to Clinical Failure Related to CAP

Characteristics CAP-Related Clinical Failure(n = 54) All Others (n = 446) p Value Missing, No.
Demographics
Male 52 (96) 437 (98) 0.432 0
Age, yr 74.3 ± 10.6 68.8 ± 12.4 0.002 0
Age > 65 yr 45 (83) 281 (63) 0.004
Current tobacco smoker 19 (35) 192 (43) 0.271 0
Comorbidities
Immunosuppression! 12 (22) 71 (16) 0.242 0
Arterial hypertension 41 (76) 309 (69) 0.316 0
Congestive heart failure 22 (41) 109 (24) 0.011 0
COPD 25 (46) 223 (50) 0.607 0
Diabetes mellitus 24 (44) 158 (35) 0.195 0
Coronary artery disease 30 (56) 185 (42) 0.051 0
Cerebrovascular accident 7(13) 51 (11) 0.741 0
Renal disease 11 (20) 65 (15) 0.265 0
Liver disease 2(4) 14(3) 0.824 0
Malignancy! 10(19) 54(12) 0.187 0
HIV infection 1 (1.9) 6(1.3) 0.766 0
Use of steroids prior to hospital admission 1 (1.9) 15 (3.4) 0.469 0
Severity on hospital admission
PSI 124 ± 40 63 ±

4 9<0.0010PSI risk classes IV and V44 (82)246 (55)<0.001 CURB-65 scores 3, 4, and 510(19)40 (9)0.0293Altered mental status8(15)38 (9)0.1360Admission to ICU15 (28)71 (16)0.0320Severe CAP on hospital admission12 (22)43 (10)0.0070Physical findings    Temperature, °C37.1 ± 1.237.5 ± 1.10.0490Temperature a 35.6°C5 (9.3)6(1.3)0.001 Respiratory rate a 30 breaths/min8(15)43 (10)0.2390Alteration of gas exchange§31 (57)141 (32)<0.0010Hypotension]12 (22)21 (5)<0.0010Heart rate a 125 beats/min7(13)44 (10)0.4790

Table 3—Laboratory and Microbiological Values, Radiologic Findings, Treatment Data, and Outcomes According to Clinical Failure Related to CAP

Characteristics CAP-Related Clinical Failure (n = 54) All Others (n = 446) p Value Missing, No.
Laboratory values
Arterial pH < 7.35 8(19) 13 (5.4) 0.002 215
WBC
Cells/L 17.8 ± 23.6 14.9 ± 10.2 0.106 1
< 4,000 cells/L 2 (3.7) 5(1.1) 0.151
PLT
Cells/L 269 ± 166 275 ± 124 0.765 1
< 400,000 cells/L 10(19) 55 (12) 0.208
< 100,000 cells/L 9(17) 18 (4) < 0.001
Albumin
mg/L 3.2 ± 0.6 3.5 ± 0.6 0.005 44
<2.5 mg/L 7 (14) 28 (7) 0.102
Sodium < 130 mmol/L 6(11) 26 (6) 0.141 0
Hematocrit < 30% 8 (15) 24 (5) 0.010 0
Creatinine
mg/dLf 1.8 ± 1.1 1.5 ± 1.7 0.280 1
< 1.5 mg/dL 21 (39) 110 (25) 0.027
BUN
mg/dL 35 ± 27 25 ± 18 < 0.001 3
< 30 mg/dL 23 (43) 100 (23) 0.002
Microbiological
Isolated pathogens 14 (26) 91 (20) 0.347 0
S pneumoniae 4 (7.4) 33 (7.4)
Staphylococcus aureus{ 4 (7.4) 28 (6.3)§
Pseudomonas aeruginosa 4 (7.4) 6(1.4)
H influenzae 2 (3.7) 12 (2.7)
Moraxella catarrhalis 1 (1.9) 6(1.4)
Legionella spp 1 (1.9) 5(1.1)
Bordetella bronchiseptica 1 (1.9) 0 (0)
Other 1 (1.9) 15 (3.4)
Combined etiology 4 (7.4) 15 (3.4) 0.138 0
Bacteremia 2 (4.2) 14 (3.5) 0.530 0
Radiology findings on CXR
Multilobar involvement 16 (30) 115 (26) 0.544 0
Pleural effusion 16 (30) 71 (16) 0.014 0
Cavitation 1 (1.9) 3 (0.7) 0.379 0
Medical treatment during hospitalization
Empiric antimicrobial therapy in compliance 47 (87) 403 (90) 0.453 0
with the ATS/IDSA guidelines
Use of respiratory fluoroquinolone 22 (41) 165 (37) 0.617 0
Use of macrolides 28 (52) 268 (60) 0.245 0
Use of steroids 8(15) 47(11) 0.343 0
Outcomes
Time to clinical stability 6.6 ± 2.5 2.8 ± 1.9 < 0.001 0
LOS in the hospital 12.6 ± 2.9 5.3 ± 3.7 < 0.001 0

Figure 1. The timing of clinical failure related to CAP.

Figure 1. The timing of clinical failure related to CAP.

Figure 2. Multivariable logistic regression analysis for clinical failure related to CAP. Hypotension = systolic BP < 90 mm Hg or diastolic BP < 60 mm Hg; alteration of gas exchange = Pao2 < 60 mm Hg, Pao2/fraction of inspired oxygen < 300, or O2 saturation < 90%; hypothermia = temperature < 35.6°C. OR = odds ratio; CI = confidence interval.

Figure 2. Multivariable logistic regression analysis for clinical failure related to CAP. Hypotension = systolic BP < 90 mm Hg or diastolic BP < 60 mm Hg; alteration of gas exchange = Pao2 < 60 mm Hg, Pao2/fraction of inspired oxygen < 300, or O2 saturation < 90%; hypothermia = temperature < 35.6°C. OR = odds ratio; CI = confidence interval.