ABSTRACT
Background and objective
Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community‐acquired pneumonia (CAP).
Methods
This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non‐NP groups, and they were compared with respect to various clinical variables.
Results
Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non‐NP. Although the use of mechanical ventilation, vasopressor infusion, 30‐day mortality, in‐hospital mortality and clinical deterioration did not differ between the NP and non‐NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP.
Conclusion
NP affects approximately one‐tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.
Keywords: community‐acquired pneumonia, computed tomography, drainage, length of hospital stay, necrotizing
Short abstract
We investigated the clinical features of community‐acquired necrotizing pneumonia. Necrotizing change was noted in approximately 10% of the patients with community‐acquired pneumonia (CAP) and was characterized by more severe clinical manifestations and increased need for pleural drainage. Necrotizing change was a predictor of length of hospital stay (LOS) but not of mortality in patients with CAP.
Abbreviations
- ALP
alkaline phosphatase
- ALT
alanine transaminase
- AST
aspartate aminotransferase
- BMI
body mass index
- BUN
blood urea nitrogen
- CAP
community‐acquired pneumonia
- CCI
Charlson co‐morbidity index
- CRP
C‐reactive protein
- CT
computed tomography
- CURB‐65
a six‐point score, one point for each of confusion, urea >7 mmol/L, respiratory rate ≥30/min, low systolic (<90 mm Hg) or diastolic (≤60 mm Hg) blood pressure and age ≥65 years
- ECOG
Eastern Cooperative Oncology Group performance status
- ESR
erythrocyte sedimentation rate
- FiO2
inspired oxygen fraction
- Hb
haemoglobin
- HR
hazard ratio
- ICU
intensive care unit
- Ig
immunoglobulin
- IQR
interquartile range
- KNUH
Kyungpook National University Hospital
- LOS
length of hospital stay
- MRSA
methicillin‐resistant Staphylococcus aureus
- NP
necrotizing pneumonia
- NT‐proBNP
N‐terminal of prohormone brain natriuretic peptide
- PaCO2
partial pressure of carbon dioxide in arterial blood
- PaO2
partial pressure of oxygen in arterial blood
- PCR
polymerase chain reaction
- PSI
pneumonia severity index
- WBC
white blood cell
INTRODUCTION
Necrotizing pneumonia (NP) is characterized by pulmonary inflammation with consolidation, peripheral necrosis and formation of multiple cavitary lesions.1 Toxins of invasive pathogens, vasculitis and venous thrombosis have been suggested to be involved in the perturbations of bronchial and pulmonary vascular supply, preceding necrotic change of lung parenchyma.2, 3 Tissue necrosis disrupts the delivery of antibiotics to infected lung areas and causes persisting infection and progressive destruction of the pulmonary parenchyma, resulting in bronchopleural fistula, empyema, septic shock and pulmonary gangrene, which are regarded as markers of the final stage of progressive lung destruction.1, 2 Furthermore, NP was considered as a rare and severe complication of bacterial community‐acquired pneumonia (CAP).1, 2, 4, 5
On chest radiographs, NP manifests as a rapid progression of airspace disease with development of cavities.1, 6 However, plain chest radiography is an inadequate diagnostic tool because it underestimates parenchymal destruction.2 Computed tomography (CT) scan with contrast enhancement provides the most sensitive diagnostic modality and is a standard procedure for the diagnosis of NP.6 On CT scans, NP is characterized by pneumonic consolidation with multiple areas of necrosis of the lung parenchyma.2, 7, 8 As described above, the detection of NP in imaging studies might raise concerns of poor prognosis and subsequent treatment failure. However, studies using CT scans for the diagnosis of NP for a large number of patients, especially in adults, are scarce.5 In addition, data regarding the incidence of NP and the differences between NP and non‐NP are limited.6 The aim of the present study was to determine the incidence of NP among CAP patients and to compare the clinical variables of patients with or without NP, and thereby to elucidate the prognostic role of necrotizing change in these patients.
METHODS
Study design
Consecutive CAP patients admitted to and treated at the Respiratory Department of Kyungpook National University Hospital (KNUH), a tertiary referral centre, in Daegu, Korea, between January 2011 and December 2014, were identified using the CAP patient registry. All patients were enrolled on admission and baseline characteristics were recorded, although not all patients underwent the same laboratory tests. Pneumonia was diagnosed using the following criteria: (i) a new radiographical infiltrate and (ii) one or more compatible symptoms or signs (cough, sputum, dyspnoea, fever and/or pleuritic chest pain). The exclusion criteria for CAP applied were as follows: (i) hospital‐acquired pneumonia or healthcare‐associated pneumonia,9 (ii) the presence of an active thoracic malignancy and (iii) immunosuppression or steroid use ( >15 mg/day of prednisone for >14 days).
Two chest radiologists (K.‐M.S. and J.‐K.L) independently reviewed the CT scan images of all patients for the presence of necrotizing changes. NP was defined as consolidation with multiple areas of non‐enhancement without rim enhancement on contrast‐enhanced CT scan in one or more pulmonary segments or lobes.10, 11 Patients without an available enhanced CT scan at presentation were excluded. Patients were allocated into NP or non‐NP group, based on the presence or absence of necrotizing changes. Clinical parameters were compared between the two groups.
The present study was approved by the Institutional Review Board of the KNUH (2015‐07‐035), which waived the requirement for written informed consent from patients owing to the retrospective nature of the study.
Data collection
Two chest physicians (H.S. and S.‐I.C.) analysed the data. Symptoms, vital signs, co‐morbid conditions, pneumonia severity indices (PSIs)12 and CURB‐65 scores13 (a six‐point score, one point for each of confusion, urea >7 mmol/L, respiratory rate ≥30/min, low systolic (<90 mm Hg) or diastolic (≤60 mm Hg) blood pressure and age ≥65 years) were reviewed. Baseline data were initially recorded by resident physicians and confirmed by attending chest physicians. Charlson co‐morbidity indices (CCIs)14 were calculated retrospectively. Information about therapeutic interventions, including mechanical ventilation, corticosteroid use, vasopressor infusion and pleural drainage with percutaneous catheters or chest tubes was collected. Length of hospital stay (LOS), admission to an intensive care unit (ICU), 30‐day mortality, in‐hospital mortality and clinical deterioration were selected as outcome variables. Clinical deterioration was defined as the initiation of mechanical ventilation, vasopressor infusion, ICU admission and 30‐day or in‐hospital mortality.
Laboratory data, including complete blood cell counts, erythrocyte sedimentation rate (ESR), liver function testing, C‐reactive protein (CRP), procalcitonin, N‐terminal of prohormone brain natriuretic peptide, blood urea nitrogen, creatinine and arterial blood gas analysis data, were reviewed.
Microbiological data
A causative pathogen was considered if one of the following criteria were met: isolation of a microorganism from blood or pleural fluid; positive urinary antigen test for Streptococcus pneumoniae or Legionella pneumophila serogroup 1 (Table S1, Supplementary Information); identification of bacteria from a sputum sample (>25 neutrophils and <10 squamous epithelial cells per lower power field) collected within 24 h of admission plus compatible Gram‐stain finding; positivity for Mycoplasma pneumoniae or Chlamydia pneumoniae as determined by a positive IgM result or a fourfold increase in IgG levels between the initial and convalescent samples (Table S1, Supplementary Information); positivity for respiratory viruses in a throat or nasopharyngeal swab by multiplex PCR (Table S1, Supplementary Information); or identification of Influenza A or B antigen or Influenza H1N1 in a throat swab (Table S1, Supplementary Information). The potentially drug‐resistant pathogens detected included methicillin‐resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and extended‐spectrum β‐lactamase‐producing Enterobacteriaceae.
Statistical analysis
Statistical analysis was performed using IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, NY, USA). P‐values <0.05 were considered statistically significant. Data were expressed as means ± SDs or medians (interquartile ranges, IQRs) for non‐normally distributed continuous variables and as numbers and percentages for categorical variables. Continuous variables were compared using the Student's t‐test or the Mann–Whitney U‐test if non‐normally distributed, whereas categorical variables were compared using the chi‐square test or Fisher's exact test. LOS was analysed using the Kaplan–Meier method; patients who died were censored from this analysis. Independent prognostic factors of LOS were identified using a stepwise forward Cox regression model.
RESULTS
Baseline characteristics
Initially, 1139 CAP patients were identified, and of these, 309 patients without available enhanced CT scans (10 patients had no CT scan images and 299 had non‐enhanced CT scan images only) were excluded. Consequently, 830 patients were included in this study; 103 (12.4%) were allocated to the NP group and 727 (87.6%) to the non‐NP group. Patients with NP were demographically characterized by a higher percentage of males, ever‐smokers and heavy drinkers compared with the non‐NP group (Table 1). Co‐morbid conditions (Table S2, Supplementary Information)—gastrectomy, diabetes and chronic liver disease—were more common in the NP group. However, CCIs did not differ significantly between the two groups.
Table 1.
Baseline characteristics of the patients
| Characteristics | NP (n = 103) | Non‐NP (n = 727) | P‐value |
|---|---|---|---|
| Age (years) | 64 (56–72) | 67 (52–76) | 0.602 |
| Male | 79 (76.7) | 448 (61.6) | 0.003 |
| BMI (kg/m2) | 21.2 (19.1–24.2) | 22.0 (19.7–24.2) | 0.257 |
| Smoking | |||
| Ever‐smoker | 72 (69.9) | 366 (50.4) | <0.001 |
| Pack‐years | 30 (20–50) | 30 (20–40) | 0.338 |
| Heavy drinking† | 23 (22.3) | 103 (14.2) | 0.031 |
| Charlson co‐morbidity index | 1 (0–1) | 0 (0–1) | 0.165 |
| ECOG | 1 (1–2) | 1 (1–1) | <0.001 |
| ECOG (3–4) | 13 (12.6) | 80 (11.0) | 0.626 |
| Systolic blood pressure (mm Hg) | 127 (113–142) | 128 (112–147) | 0.998 |
| Pulse rate (/min) | 101 (88–116) | 94 (83–107) | 0.002 |
| Respiratory rate (/min) | 20 (19–22) | 20 (18–21) | 0.063 |
| Symptoms | |||
| Duration of symptom (days) | 7 (5–14) | 5 (3–7) | <0.001 |
| Cough | 92 (89.3) | 626 (86.1) | 0.372 |
| Sputum production | 67 (65.0) | 500 (68.8) | 0.372 |
| Dyspnoea | 74 (72.5) | 383 (52.8) | <0.001 |
| Fever | 78 (75.7) | 453 (62.3) | 0.008 |
| Altered mental status | 2 (1.9) | 29 (4.0) | 0.413 |
| Haemoptysis | 16 (15.5) | 63 (8.7) | 0.027 |
| Chest pain | 70 (68.0) | 176 (24.2) | <0.001 |
| CURB‐65 | 1 (0–2) | 1 (0–2) | 0.480 |
| CURB‐65 (3–5) | 8 (7.8) | 36 (5.0) | 0.233 |
| PSI class | 3 (2–4) | 3 (2–3) | 0.002 |
| PSI class (4–5) | 34 (33) | 176 (24.2) | 0.055 |
| Complicated parapneumonic effusion or empyema | 48 (46.6) | 41 (5.6) | <0.001 |
| Pleural drainage | 57 (55.3) | 53 (7.3) | <0.001 |
| Mechanical ventilation | 4 (3.9) | 34 (4.7) | >0.999 |
| Vasopressor infusion | 8 (7.8) | 41 (5.6) | 0.391 |
| Corticosteroids | 16 (15.5) | 148 (20.4) | 0.250 |
| Admission to intensive care unit | 5 (4.9) | 42 (5.8) | 0.705 |
| 30‐day mortality | 9 (8.7) | 39 (5.4) | 0.170 |
| In‐hospital mortality | 6 (5.8) | 35 (4.8) | 0.658 |
| Length of hospital stay (days) | 14 (11–16) | 8 (6–12) | <0.001 |
| Clinical deterioration | 14 (13.6) | 75 (10.3) | 0.315 |
Data are presented as median (interquartile range) or n (%).
Heavy drinking is defined as the consumption of seven or more drinks (>60 g of alcohol) on one occasion for males, and five or more drinks (>40 g of alcohol) on one occasion for females at least twice a week.
CURB‐65, a six‐point score, one point for each of confusion, urea >7 mmol/L, respiratory rate ≥30/min, low systolic (<90 mm Hg) or diastolic (≤60 mm Hg) blood pressure and age ≥65 years; ECOG, Eastern Cooperative Oncology Group performance status; NP, necrotizing pneumonia; PSI, pneumonia severity index.
Patients in the NP group experienced significantly more symptoms, including dyspnoea, fever, haemoptysis and chest pain, than patients in the non‐NP group. CURB‐65 scores and high CURB‐65 (3–5) rates were similar in the two groups, but PSI class was significantly higher (3 (2–4) vs 3 (2–3), P = 0.002) and a high PSI class (4–5) tended to be more common (34 (33%) vs 176 (24%), P = 0.055) in the NP group. Pleural drainage was performed significantly more often in the NP group (57 (55%) vs 53 (7%), P < 0.001). No intergroup differences were noted for the use of mechanical ventilation, vasopressor infusion, ICU admission, 30‐day mortality, in‐hospital mortality or clinical deterioration. In contrast, median LOS was significantly longer in the NP group (14 days (11–16 days) vs 8 days (6–12 days), P < 0.001).
Blood laboratory findings
Inflammatory markers, including white blood cell count, ESR and CRP, were significantly higher and the levels of serum albumin and sodium were significantly lower in the NP group (Table 2).
Table 2.
Blood laboratory findings of the patients
| Parameters | NP | n | Non‐NP | n | P‐value |
|---|---|---|---|---|---|
| WBC count (/μL) | 14 970 (11 030–18 780) | 103 | 10 130 (7485–13 910) | 727 | <0.001 |
| ESR (mm/h) | 70 (50–92) | 103 | 48 (29–67) | 726 | <0.001 |
| C‐reactive protein (mg/dL) | 18.8 (12.0–25.5) | 103 | 11.4 (6.1–18.9) | 724 | <0.001 |
| NT‐proBNP (pg/mL) | 249.0 (135.8–812.0) | 100 | 335.0 (119.3–1085.0) | 656 | 0.422 |
| Hb (g/dL) | 11.9 ± 1.9 | 103 | 12.6 ± 1.7 | 727 | 0.001 |
| Platelet (103/μL) | 340 (263–466) | 103 | 237 (184–313) | 727 | <0.001 |
| Albumin (g/dL) | 2.9 (2.4–3.3) | 103 | 3.4 (3.0–3.8) | 727 | <0.001 |
| Total protein (g/dL) | 6.3 (5.8–6.9) | 103 | 6.5 (6.1–7.0) | 727 | 0.004 |
| Total bilirubin (mg/dL) | 0.58 (0.41–0.96) | 103 | 0.60 (0.39–0.88) | 726 | 0.255 |
| AST (U/L) | 25 (18–45) | 103 | 25 (18–37) | 726 | 0.533 |
| ALT (U/L) | 22 (14–37) | 103 | 20 (13–31) | 726 | 0.173 |
| ALP (U/L) | 101 (78–136) | 103 | 77 (62–104) | 724 | <0.001 |
| BUN (mg/dL) | 14.0 (10.3–18.1) | 103 | 14.3 (10.6–19.9) | 727 | 0.612 |
| Creatinine (mg/dL) | 0.77 (0.63–0.94) | 103 | 0.83 (0.68–1.03) | 727 | 0.029 |
| Sodium (mmol/L) | 135 (132–137) | 103 | 137 (134–139) | 727 | 0.001 |
| PaO2/FiO2 | 345.3 (287.7–394.6) | 92 | 342.1 (286.0–404.3) | 613 | 0.755 |
| PaCO2 | 27.4 (24.4–31.5) | 92 | 28.9 (26.5–32.6) | 613 | 0.002 |
Data are presented as mean ± SD, median (interquartile range) or n (%).
ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; ESR, erythrocyte sedimentation rate; FiO2, inspired oxygen fraction; LDH, lactate dehydrogenase; NP, necrotizing pneumonia; NT‐proBNP, N‐terminal of prohormone brain natriuretic peptide; PaCO2, partial pressure of carbon dioxide in arterial blood; PaO2, partial pressure of oxygen in arterial blood; SD, standard deviation; WBC, white blood cell.
Microbiological data and antimicrobial treatment
In the NP group, 37 pathogens were identified in 27 patients (26%), and in the non‐NP group, 283 pathogens were identified in 218 patients (30%) (Table 3). The most common pathogen in the NP group was Klebsiella pneumoniae (n = 9), followed by S. pneumoniae (n = 5) and S. aureus (n = 5). Klebsiella pneumoniae (9 (33%) vs 38 (17%), P = 0.048), S. aureus (5 (19%) vs 12 (6%), P = 0.012) and Streptococcus milleri group (4 (15%) vs 3 (1%), P = 0.003) were significantly more common in the NP group, whereas M. pneumoniae (3 (11%) vs 79 (36%), P = 0.009) was significantly less common. On the other hand, the frequencies of potentially drug‐resistant pathogens were similar in the two groups.
Table 3.
Microbiological diagnosis
| NP (n = 27) | Non‐NP (n = 218) | P‐value | |
|---|---|---|---|
| Streptococcus pneumoniae | 5 (18.5) | 75 (34.4) | 0.097 |
| Streptococcus milleri group | 4 (14.8) | 3 (1.4) | 0.003 |
| Streptococcus constellatus | 2 | 2 | |
| Streptococcus intermedius | 2 | 1 | |
| Other viridans streptococci | 1 (3.7) | 5 (2.3) | 0.508 |
| Streptococcus mitis/oralis | 1 | 4 | |
| Streptococcus sanguis | 0 | 1 | |
| Other streptococcus species | 2 (7.4) | 5 (2.3) | 0.174 |
| α‐Haemolytic | 0 | 2 | |
| Streptococcus agalactiae | 1 | 1 | |
| Not specified | 1 | 2 | |
| Staphylococcus aureus | 5 (18.5) | 12 (5.5) | 0.012 |
| Methicillin‐susceptible | 5 | 10 | |
| Methicillin‐resistant | 0 | 2 | |
| Klebsiella pneumoniae | 9 (33.3) | 38 (17.4) | 0.048 |
| Pseudomonas aeruginosa | 3 (11.1) | 14 (6.4) | 0.412 |
| Acinetobacter baumannii | 1 (3.7) | 8 (3.7) | >0.999 |
| Enterobacter cloacae | 1 (3.7) | 0 (0) | 0.110 |
| Escherichia coli | 1 (3.7) | 3 (1.4) | 0.375 |
| Stenotrophomonas maltophilia | 1 (3.7) | 1 (0.5) | 0.209 |
| Proteus mirabilis | 0 (0) | 1 (0.5) | >0.999 |
| Hemophilus influenzae | 0 (0) | 4 (1.8) | >0.999 |
| Morganella morgagnii | 0 (0) | 1 (0.5) | >0.999 |
| Serratia marcescens | 0 (0) | 1 (0.5) | >0.999 |
| Mycoplasma pneumoniae | 3 (11.1) | 79 (36.2) | 0.009 |
| Chlamydia pneumoniae | 1 (3.7) | 7 (3.2) | >0.999 |
| Legionella pneumophila | 0 (0) | 7 (3.2) | >0.999 |
| Virus | 0 (0) | 19 (8.7) | 0.241 |
| Adenovirus | 0 | 2 | |
| Influenza A | 0 | 11 | |
| Metapneumovirus | 0 | 1 | |
| Respiratory syncytial virus‐A | 0 | 2 | |
| Respiratory syncytial virus‐B | 0 | 1 | |
| Rhinovirus A | 0 | 1 | |
| Coronavirus 229E/NL63 | 0 | 1 | |
| Potentially drug‐resistant pathogens† | 5 (18.5) | 29 (13.3) | 0.460 |
Data are presented as n (%).
Potentially drug‐resistant pathogens include A. baumannii, methicillin‐resistant S. aureus, extended spectrum beta‐lactamase‐producing Enterobacteriaceae, P. aeruginosa and S. maltophilia.
NP, necrotizing pneumonia.
In the NP group, ampicillin‐sulbactam with or without macrolide or fluoroquinolone (50 (49%)) was the most commonly used antibiotic regimen, followed by cefotaxime or ceftriaxone plus clindamycin (21 (20%)) (Table 4). Both regimens were administered significantly more often in the NP group (50 (49%) vs 120 (17%), P < 0.001 and 21 (20%) vs. 21 (3%), P < 0.001, respectively). Cefotaxime or ceftriaxone with or without macrolide or fluoroquinolone was less frequently administered (19 (18%) vs 490 (67%), P < 0.001) in the NP group.
Table 4.
Antimicrobial treatment
| NP (n = 103) | Non‐NP (n = 727) | P‐value | |
|---|---|---|---|
| Ampicillin‐sulbactam with or without macrolide or fluoroquinolone | 50 (48.5) | 120 (16.5) | <0.001 |
| Cefotaxime or ceftriaxone plus clindamycin | 21 (20.4) | 21 (2.9) | <0.001 |
| Cefotaxime or ceftriaxone with or without macrolide or fluoroquinolone | 19 (18.4) | 490 (67.4) | <0.001 |
| Fluoroquinolone with or without aminoglycoside | 1 (1.0) | 29 (4.0) | 0.161 |
| Antipseudomonal beta‐lactams plus fluoroquinolone or aminoglycoside | 9 (8.7) | 53 (7.3) | 0.601 |
| Meropenem plus fluoroquinolone or aminoglycoside | 1 (1.0) | 3 (0.4) | 0.412 |
| Meropenem plus vancomycin or teicoplanin | 0 (0) | 7 (1.0) | >0.999 |
| Others† | 2 (1.9) | 4 (0.6) | 0.164 |
Data are presented as n (%).
Others include antipseudomonal beta‐lactam plus fluoroquinolone plus teicoplanin (n = 3), antipseudomonal beta‐lactam plus teicoplanin (n = 1), vancomycin plus clindamycin (n = 1) and teicoplanin plus moxifloxacin (n = 1).
NP, necrotizing pneumonia.
Factors affecting LOS
As mentioned above, LOS was the only outcome variable that differed significantly between the two groups. Kaplan–Meier curve was constructed for the NP and non‐NP groups (Fig. 1). Patients with NP were significantly more likely to stay longer in hospital compared to those without NP (log‐rank P < 0.001 and Breslow P < 0.001). Thus, we tried to identify factors associated with LOS. We set up two models based on two clinical prediction scores, that is, PSI and CURB‐65 (Table 5). By multivariate analysis using the CURB‐65‐based Cox proportional hazards model, necrotizing change (hazard ratio (HR): 1.56, 95% CI: 1.24–1.97, P < 0.001), CCI of ≥1 (HR: 1.41, 95% CI: 1.22–1.62, P < 0.001), high CURB‐65 (HR: 2.48, 95% CI: 1.70–3.62, P < 0.001) and pleural drainage (HR: 1.63, 95% CI: 1.30–2.05, P < 0.001) (Table 5) were found to predict LOS independently. According to the PSI‐based model, NP (HR: 1.52, 95% CI: 1.20–1.92, P < 0.001), high PSI (HR: 1.85, 95% CI: 1.56–2.20, P < 0.001) and pleural drainage (HR 1.64, 95% CI 1.30–2.06, P < 0.001) independently predicted LOS.
Figure 1.
Kaplan–Meier curves showing time to discharge in patients with necrotizing pneumonia (NP, solid line) or non‐NP (dashed line; log‐rank P < 0.001 and Breslow P < 0.001). + denotes censored data.
Table 5.
Variables influencing the length of hospital stay
| Univariate analysis | Multivariate analysis | |||||
|---|---|---|---|---|---|---|
| P‐value | HR | 95% CI | P‐value | HR | 95% CI | |
| CURB‐65‐based model | ||||||
| Female | 0.002 | 0.80 | 0.69–0.92 | 0.386 | 0.91 | 0.74–1.13 |
| Ever‐smoker | 0.005 | 1.23 | 1.06–1.41 | 0.503 | 0.93 | 0.76–1.15 |
| Heavy drinking | 0.010 | 1.29 | 1.06–1.57 | 0.312 | 1.11 | 0.90–1.37 |
| CCI ≥ 1 | <0.001 | 1.34 | 1.17–1.55 | <0.001 | 1.41 | 1.22–1.62 |
| CURB‐65 (3–5) | <0.001 | 2.48 | 1.71–3.61 | <0.001 | 2.48 | 1.70–3.62 |
| Pleural drainage | <0.001 | 1.93 | 1.57–2.38 | <0.001 | 1.63 | 1.30–2.05 |
| NP | <0.001 | 1.88 | 1.52–2.33 | <0.001 | 1.56 | 1.24–1.97 |
| PSI‐based model | ||||||
| Ever‐smoker | 0.005 | 1.23 | 1.06–1.41 | 0.953 | 0.99 | 0.86–1.16 |
| Heavy drinking | 0.010 | 1.29 | 1.06–1.57 | 0.383 | 1.10 | 0.89–1.35 |
| PSI (4–5) | <0.001 | 1.82 | 1.54–2.16 | <0.001 | 1.85 | 1.56–2.20 |
| Pleural drainage | <0.001 | 1.93 | 1.57–2.38 | <0.001 | 1.64 | 1.30–2.06 |
| NP | <0.001 | 1.88 | 1.52–2.33 | <0.001 | 1.52 | 1.20–1.92 |
CCI, Charlson co‐morbidity index; CI, confidence interval; CURB‐65, a six‐point score, one point for each of confusion, urea >7 mmol/L, respiratory rate ≥30/min, low systolic (<90 mm Hg) or diastolic (≤60 mm Hg) blood pressure and age ≥65 years; HR, hazard ratio; NP, necrotizing pneumonia; PSI, pneumonia severity index.
DISCUSSION
In the present study, NP accounted for 12% of hospitalized CAP patients and it was characterized by higher frequency of symptoms, higher PSI class, higher levels of inflammatory markers and more frequent need for pleural drainage, which suggested that patients with NP experience a more severe clinical course. The most common pathogen of community‐acquired NP was K. pneumoniae, followed by S. aureus, S. pneumoniae and S. milleri group. In patients hospitalized with CAP, the development of necrotizing changes influenced LOS, but it did not affect 30‐day mortality or in‐hospital mortality.
NP is considered a rare complication of bacterial lung infection;2 however, information regarding the proportion of NP in CAP patients affected is limited. The presence of parenchymal lung lesions, a requisite for the diagnosis of pneumonia, is usually based on new infiltrates on chest radiograph.15 However, because chest radiograph is often insufficient for detecting pulmonary parenchymal lesions of pneumonia, chest CT scan can improve the diagnosis of CAP.16, 17 At our institution, emergency physicians who saw patients with suspected pneumonia tended to confirm pneumonia to transfer them from the Emergency Department to the Internal Medicine Department. Therefore, although CT scan is usually not necessary for the diagnosis of CAP, it was used in the majority of CAP patients treated at our institution, which allowed us to determine the proportion of patients with NP. Therefore, these facts are likely to reduce the possibility that patients who underwent CT scan had more severe disease. In the present study, NP was observed in approximately 12% of the hospitalized CAP patients. Similarly, in a previous study, 136 (39%) of 351 patients with pneumococcal pneumonia underwent CT scan of the chest, and necrotizing changes in the lungs were observed in 11% (n = 15).6
The reasons behind a microbial agent causing necrotizing changes in the lung parenchyma of one patient but not in another remain to be elucidated.1 One possible explanation could be the differences in the general condition or immune status of the patients. In the present study, NP was demographically characterized by a higher number of males, ever‐smokers and heavy drinkers, and was more commonly associated with post‐gastrectomy status, chronic liver disease and diabetes. This is consistent with a previous review that reported alcoholism and diabetes as common co‐morbid conditions commonly accompanying NP.2 The duration of symptoms in the NP group was significantly longer than that in the non‐NP group, suggesting that delayed treatment could facilitate necrotizing changes.
As noted in a previous review,2 NP was associated with more symptoms of pneumonia and unfavourable laboratory data, including higher levels of inflammatory markers. However, in the present study, these clinical features of NP were not associated with 30‐day or in‐hospital mortality, which suggests that NP severity perse does not increase the risk of mortality. In the same context, mechanical ventilation, vasopressor therapy and clinical deterioration rates were similar in the two groups. Interestingly, the two clinical prediction scoring systems showed conflicting results; median PSI class was higher in the NP group but median CURB‐65 scores were similar in both groups. In fact, LOS was the only clinical endpoint that allowed to differentiate the two groups. Multivariate analysis showed that necrotizing changes independently predicted LOS. The longer LOS observed in the NP group could be explained as follows: (i) more severe inflammation, reflected by higher blood levels of inflammatory markers; (ii) impaired blood supply to the pulmonary parenchyma, leading to impediment of antibiotic delivery;2, 18, 19 and (3) more frequent association with complicated parapneumonic effusion or empyema requiring pleural drainage.
The aetiology of NP has not been previously studied in a large patient cohort. Classically, anaerobes were considered to be among the more important pathogens, and were believed to cause a spectrum of aspiration syndromes, including aspiration pneumonia, lung abscess and empyema.10, 20, 21 Pleural fluid and transthoracic needle aspirates are the only sources of specimens currently available for obtaining meaningful anaerobic cultures from patients with NP.22 In the present study, no anaerobes were cultured from blood and pleural fluid of NP patients. The most common microbe was K. pneumoniae, followed by S. aureus, S. pneumoniae and S. milleri group. These findings corresponds with those of other studies, in which S. pneumoniae, S. aureus and K. pneumoniae were common in patients with severe NP requiring surgical intervention.1, 4, 23, 24 The rates of potentially drug‐resistant pathogens were similar in our NP and non‐NP groups in the present study.
Several limitations of the present study should be noted. First, it is limited by its retrospective design and because it was conducted in a single institution, the possibility of selection bias has to be considered. Furthermore, because some CAP patients were treated at other departments in our institution, not all CAP patients were enrolled in the present study, and not all CAP patients underwent enhanced CT scan, although many (74%) did. Second, no microbiological study was performed on anaerobes from lung tissues or aspirates, and thus, the possibility that anaerobes were not identified as causative agents should be considered. Moreover, due to the retrospective nature of this study, all patients did not undergo the same tests for the aetiological agents, including atypical pathogens. Finally, decisions regarding treatment including antibiotics depended on attending physicians. For these reasons, we acknowledge that a larger prospective study should be undertaken to confirm our findings.
In conclusion, NP, which affected 12% of the CAP patients in the present study, was associated with more severe clinical manifestations and more frequent need to perform pleural drainage. NP differed microbiologically from non‐NP. Interestingly, necrotizing change on CT scan images was associated with longer LOS, but not with mortality in our patient cohort.
Supporting information
Table S1 Methods of microbiological diagnosis.
Table S2 Co‐morbidities of the patients.
Seo, H. , Cha, S.‐I. , Shin, K.‐M. , Lim, J.‐K. , Yoo, S.‐S. , Lee, J. , Lee, S.‐Y. , Kim, C.‐H. , Park, J.‐Y. and Lee, W.‐K. (2016) Clinical relevance of necrotizing change in patients with community‐acquired pneumonia. Respirology, 22: 551–558. doi: 10.1111/resp.12943.
(Associate Editor: Marcos Restrepo)
REFERENCES
- 1. Chatha N, Fortin D, Bosma KJ. Management of necrotizing pneumonia and pulmonary gangrene: a case series and review of the literature. Can. Respir. J. 2014; 21: 239–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Tsai YF, Ku YH. Necrotizing pneumonia: a rare complication of pneumonia requiring special consideration. Curr. Opin. Pulm. Med. 2012; 18: 246–52. [DOI] [PubMed] [Google Scholar]
- 3. Hammond JM, Lyddell C, Potgieter PD, Odell J. Severe pneumococcal pneumonia complicated by massive pulmonary gangrene. Chest 1993; 104: 1610–2. [DOI] [PubMed] [Google Scholar]
- 4. Tsai YF, Tsai YT, Ku YH. Surgical treatment of 26 patients with necrotizing pneumonia. Eur. Surg. Res. 2011; 47: 13–8. [DOI] [PubMed] [Google Scholar]
- 5. Sawicki GS, Lu FL, Valim C, Cleveland RH, Colin AA. Necrotising pneumonia is an increasingly detected complication of pneumonia in children. Eur. Respir. J. 2008; 31: 1285–91. [DOI] [PubMed] [Google Scholar]
- 6. Pande A, Nasir S, Rueda AM, Matejowsky R, Ramos J, Doshi S, Kulkarni P, Musher DM. The prevalence of necrotizing changes in adults with pneumococcal pneumonia. Clin. Infect. Dis. 2013; 54: 10–6. [DOI] [PubMed] [Google Scholar]
- 7. Hodina M, Hanquinet S, Cotting J, Schnyder P, Gudinchet F. Imaging of cavitary necrosis in complicated childhood pneumonia. Eur. Radiol. 2002; 12: 391–6. [DOI] [PubMed] [Google Scholar]
- 8. Moon WK, Im JG, Yeon KM, Han MC. Complications of Klebsiella pneumonia: CT evaluation. J. Comput. Assist. Tomogr. 1995; 19: 176–81. [DOI] [PubMed] [Google Scholar]
- 9.Niderman MS, Craven DE, Bonten MJ, Chastre J, Craig WA, Fagon JY, Hall J, Jacoby GA, Kollef MH, Luna CM, et al Guidelines for the management of adults with hospital‐acquired, ventilator‐associated, and healthcare‐associated pneumonia. Am. J. Respir. Crit. Care Med. 2005; 171: 388–416. [DOI] [PubMed] [Google Scholar]
- 10. Hill MK, Sanders CV. Anaerobic disease of the lung. Infect. Dis. Clin. North Am. 1991; 5: 453–66. [PubMed] [Google Scholar]
- 11. Hoffer FA, Bloom DA, Colin AA, Fishman SJ. Lung abscess versus necrotizing pneumonia: implications for interventional therapy. Pediatr. Radiol. 1999; 29: 87–91. [DOI] [PubMed] [Google Scholar]
- 12. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN. A prediction rule to identify low‐risk patients with community‐acquired pneumonia. N. Engl. J. Med. 1997; 336: 243–50. [DOI] [PubMed] [Google Scholar]
- 13. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, Lewis SA, Macfarlane JT. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003; 58: 377–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 1987; 40: 373–83. [DOI] [PubMed] [Google Scholar]
- 15. Lim WS, Baudouin SV, Macfarlane JT; British Thoracic Society Community Acquired Pneumonia Guidelines Committee . Community acquired pneumonia. Management in primary care. BMJ 2010; 341: c4469. [DOI] [PubMed] [Google Scholar]
- 16. Syrjälä H, Broas M, Suramo I, Ojala A, Lähde S. High‐resolution computed tomography for the diagnosis of community‐acquired pneumonia. Clin. Infect. Dis. 1998; 27: 358–63. [DOI] [PubMed] [Google Scholar]
- 17. Claessens YE, Debray MP, Tubach F, Brun AL, Rammaert B, Hausfater P, Naccache JM, Ray P, Choquet C, Carette MF et al. Early chest computed tomography scan to assist diagnosis and guide treatment decision for suspected community‐acquired pneumonia. Am. J. Respir. Crit. Care Med. 2015; 192: 974–82. [DOI] [PubMed] [Google Scholar]
- 18. Chen CH, Huang WC, Chen TY, Hung TT, Liu HC, Chen CH. Massive necrotizing pneumonia with pulmonary gangrene. Ann. Thorac. Surg. 2009; 87: 310–1. [DOI] [PubMed] [Google Scholar]
- 19. Curry CA, Fishman EK, Buckley JA. Pulmonary gangrene: radiologic and pathologic correlation. South. Med. J. 1998; 91: 957–60. [PubMed] [Google Scholar]
- 20. Pennza PT. Aspiration pneumonia, necrotizing pneumonia, and lung abscess. Emerg. Med. Clin. North Am. 1989; 7: 279–307. [PubMed] [Google Scholar]
- 21. Fernandez‐Sabe N, Carratala J, Dorca J, Roson B, Tubau F, Manresa F, Gudiol F. Efficacy and safety of sequential amoxicillin‐clavulanate in the treatment of anaerobic lung infections. Eur. J. Clin. Microbiol. Infect. Dis. 2003; 22: 185–7. [DOI] [PubMed] [Google Scholar]
- 22. Bartlett JG. Anaerobic bacterial infection of the lung. Anaerobe 2012; 18: 235–9. [DOI] [PubMed] [Google Scholar]
- 23. Krishnadasan B, Sherbin VL, Vallieres E, Karmy‐Jones R. Surgical management of lung gangrene. Can. Respir. J. 2000; 7: 401–4. [DOI] [PubMed] [Google Scholar]
- 24. Reimel BA, Krishnadasen B, Cuschieri J, Klein MB, Gross J, Karmy‐Jones R. Surgical management of acute necrotizing lung infections. Can. Respir. J. 2006; 13: 369–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Supplementary Materials
Table S1 Methods of microbiological diagnosis.
Table S2 Co‐morbidities of the patients.