Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses. STUDY DESIGN AND METHODS: We analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone. RESULTS: Of the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29-0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32-2.36). CONCLUSIONS: Corticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.

Aspiration pneumonia.

The growing population of older people worldwide represents a great challenge for health systems. The elderly are at increased risk of infectious diseases such as pneumonia, which is associated with increased morbidity and mortality related mainly to age-related physiological changes in the immune system (immunosenescence), the presence of multiple chronic comorbidities, and frailty. In pneumonia, microaspiration is recognized as the main pathogenic mechanism; while macroaspiration which refers to the aspiration of a large amount of oropharyngeal or upper gastrointestinal content passing through the vocal cords and trachea into the lungs is identified as "aspiration pneumonia". Although there are strategies for the prevention and management of patients with pneumonia that have been shown to be effective in older people with pneumonia, more research is needed on aspiration pneumonia, its risk factors and outcomes, especially since there are no specific criteria for its diagnosis and consequently, the studies on aspiration pneumonia include heterogeneous populations.

Fluoroquinolones in the management of community-acquired pneumonia.

AIMS: Review of the current guidelines for the use of respiratory fluoroquinolones in the management of community-acquired pneumonia (CAP). METHODS: Data were collected from recent clinical trials on fluoroquinolone therapy in patients with CAP and from updated recommendations of antimicrobial therapy in managing CAP, with a focus on current North American guidelines. RESULTS: Randomised clinical trials of respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) in the treatment of CAP were identified and analysed. The bacteriology of CAP, and susceptibility rates, resistance rates and pharmacokinetic and pharmacodynamic properties of fluoroquinolones against causative pathogens in CAP, and adverse event profiles of these agents were described. Respiratory fluoroquinolones have broad-spectrum antibacterial activities against common causative pathogens in CAP and provide an important treatment option as monotherapy for outpatients with comorbidities and inpatients who are not admitted to the intensive care unit (ICU), including those with risk factors of drug-resistant Streptococcus pneumoniae. For treatment of ICU patients with severe CAP, it is recommended that fluoroquinolones be used in combination with a beta-lactam. Recent studies also demonstrated a more rapid resolution of clinical symptoms with the use of highly potent respiratory fluoroquinolones. DISCUSSION: Appropriate use of fluoroquinolone agents may shorten the duration of antimicrobial therapy and the length of hospital stay and contribute to the decreased development of resistance in patients with CAP. Adverse event profiles of these agents should be considered to facilitate the selection of an appropriate fluoroquinolone for appropriate CAP patients. CONCLUSION: The fluoroquinolone class, specifically those with adequate activity against respiratory pathogens, represents an important and convenient treatment option for patients with CAP.

Hospitalization due to community-acquired pneumonia in patients with chronic obstructive pulmonary disease: incidence, epidemiology and outcomes.

OBJECTIVES: Community-acquired pneumonia (CAP) is an important complication in patients with chronic obstructive pulmonary disease (COPD). This study aimed to define incidence, and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, and to estimate the burden of disease in the US population. METHODS: This was a secondary analysis of a prospective population-based cohort study of residents in Louisville, Kentucky, 40 years old and older, from 1 June 2014 to 31 May 2016. All adults hospitalized with CAP were enrolled. The annual incidence of pneumonia in COPD patients in Louisville was calculated and the total number of adults with COPD hospitalized in the United States was estimated. Clinical outcomes included time to clinical stability (TCS), length of hospital stay (LOS) and mortality. RESULTS: From a Louisville population of 18 246 patients with COPD, 3419 pneumonia hospitalizations were documented during the 2-year study. The annual incidence was 9369 patients with pneumonia per 100 000 COPD population, corresponding to an estimated 506 953 adults with COPD hospitalized due to pneumonia in the United States. The incidence of CAP in patients without COPD was 509 (95% CI 485-533) per 100 000. COPD patients had a median (interquartile range) TCS and LOS of 2 (1-4) and 5 (3-9) days respectively. The mortality of COPD patients during hospitalization, at 30 days, 6 months and 1 year was 193 of 3419 (5.6%), 400 of 3374 (11.9%), 816 of 3363 (24.3%) and 1104 of 3349 (33.0%), respectively. CONCLUSIONS: There was an annual incidence of 9369 cases of hospitalized CAP per 100 000 COPD patients in the city of Louisville. This was an approximately 18-fold greater incidence of CAP in COPD patients than in those without COPD.

Markers of treatment failure in hospitalised community acquired pneumonia.

BACKGROUND: Lack of response to treatment in community acquired pneumonia (CAP) worsens outcome. We evaluated the systemic cytokine profile (tumour necrosis factor alpha, interleukin (IL)1, IL6, IL8 and IL10), C reactive protein (CRP) and procalcitonin (PCT) in patients with CAP who had treatment failure. METHODS: A prospective study was performed in hospitalised patients with CAP. Cytokines, PCT and CRP measurements were obtained on day 1 and after 72 h of treatment. Treatment failure was the endpoint evaluated, with separation of those with early (< or = 72 h) or late failure. RESULTS: 453 patients were included: 84 (18%) had treatment failure, of whom 38 (8%) were early failures. Median levels of IL6, PCT and CRP on days 1 and 3 and median levels of IL8 on day 1 were significantly higher in patients with any treatment failure. Logistic regression analysis demonstrated that values above the cut-off points for IL6 (> or = 169 pg/ml), IL8 (> or = 14 pg/ml) and CRP (> or = 21.9 mg/dl) on day 1 had independent predictive value for any treatment failure after adjustment for initial severity; relative risks (OR) found were 1.9, 2.2 and 2.6, respectively. Increased levels for CRP and PCT on day 1 were also independent predictors for early failure. Increased levels for IL6 and CRP were the best predictors of late failure. CONCLUSIONS: Serum levels of CRP, IL6 and PCT on days 1 and 3 were independently associated with a higher risk of any treatment failure. Low levels of PCT and CRP on day 1 had a high negative predictive value for early failure.

Adherence to guidelines' empirical antibiotic recommendations and community-acquired pneumonia outcome.

The American Thoracic Society (ATS) published guidelines for the treatment and management of community-acquired pneumonia in 2001, but the impact of adherence on outcomes such as mortality and length of stay is not well defined. A study of 780 patients with community-acquired pneumonia consecutively admitted to hospital over 1 yr was carried out. Nursing home patients were excluded. Overall adherence to antibiotics recommended in the ATS guidelines was 84%. The lowest adherence was found in patients admitted to an intensive care unit (52%), especially those at risk of infection with Pseudomonas aeruginosa (ATS group IVb). However, very few patients from this group were indeed infected with P. aeruginosa. This could be explained by the exclusion of the nursing home patients. There was a difference in mortality between patients that received adherent and nonadherent regimens (3 versus 10.6%). There was a difference in length of stay between patients receiving adherent and nonadherent regimens (7.6 versus 10.4 days). This result was confirmed on multivariate analysis. Adherence to the 2001 American Thoracic Society guidelines was high except in community-acquired pneumonia patients admitted to an intensive care unit. Length of stay was shorter in patients who received adherent rather than nonadherent antibiotic regimens.

A prospective comparison of nursing home-acquired pneumonia with hospital-acquired pneumonia in non-intubated elderly.

There are no prospective comparison of the etiology and clinical outcome between hospital-acquired pneumonia (HAP) and nursing home-acquired pneumonia (NHAP) in non-intubated elderly. This study prospectively evaluated the etiology of HAP and NHAP in non-intubated elderly. A prospective cohort study was carried out in a rural region of Japan where the population over 65 years of age represents 30% of the population. A total of 108 patients were enrolled. There were 33 patients with HAP and 75 with NHAP. Etiologic diagnosis was established in 78.8% of HAP and in 72% of NHAP patients. The most frequent pathogens were Chlamydophila pneumoniae followed by Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus. The frequency of Streptococcus pneumoniae and Influenza virus was significantly higher, whereas the frequency of Staphylococcus aureus and Enterobacteriaceae was significantly lower in NHAP compared to HAP. Performance and nutritional status were significantly worse in patients with HAP than in those with NHAP. Hospital mortality was significantly lower in patients with NHAP compared to those with HAP. This study demonstrated that C. pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus are frequent causative agents of pneumonia in non-intubated elderly and that the responsible pathogens and clinical outcome differ between NHAP and HAP.

Multi-drug resistant organism infections in a medical ICU: Association to clinical features and impact upon outcome.

OBJECTIVE: To define clinical features associated with Intensive Care Unit (ICU) infections caused by multi-drug resistant organisms (MDRO) and their impact on patient outcome. DESIGN: A single-center, retrospective case-control study was carried out between January 2010 and May 2010. SETTING: A medical ICU (MICU) in the United States. PATIENTS: The study included a total of 127 MDRO-positive patients and 186 MDRO-negative patients. INTERVENTIONS: No interventions were carried out. RESULTS: Out of a total of 313 patients, MDROs were present in 127 (41.7%). Based on the multivariate analysis, only infection as a cause of admission [OR 3.3 (1.9-5.8)]), total days of ventilation [OR 1.07 (1.01-1.12)], total days in hospital [OR 1.04 (1.01-1.07)], immunosuppression [OR 2.04 (1.2-3.5)], a history of hyperlipidemia [OR 2.2 (1.2-3.8)], surgical history [OR 1.82 (1.05-3.14)] and age [OR 1.02 (1.00-1.04)] were identified as clinical factors independently associated to MDROs, while the Caucasian race was negatively associated to MDROs. The distribution of days on ventilation, days in hospital and days of antibiotic treatment prior to infection differed between the MDRO-positive and MDRO-negative groups. The MDRO-positive patients showed a greater median number of days in hospital and days of antibiotic treatment before infection, with a greater median number of days in hospital, days of antibiotic treatment and days of ventilation after infection, compared to the MDRO-negative patients. The mortality rate was not significantly different between the two groups. Appropriate empirical antibiotic therapy was prescribed in 82% of the MDRO-positive cases - such treatment being started within 24h after onset of the infection in 68.5% of the cases. CONCLUSION: Defining clinical factors associated with MDRO infections and administering timely and appropriate empirical antibiotic therapy may help reduce the mortality associated with these infections. In our hospital we did not withhold broad spectrum drugs as empirical therapy in patients with clinical features associated to MDRO infection. Our rate of appropriate empirical therapy was therefore high, which could explain the absence of excessive mortality in patients infected with MDROs.

Eradication of H. influenzae in AECB: A pooled analysis of moxifloxacin phase III trials compared with macrolide agents.

Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind, multicentre, randomised trials. Patients received either moxifloxacin (400 mg qd for 5-10 days) or macrolides (azithromycin 500 mg/250 mg qd for 5 days or clarithromycin 500 mg bid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P = 0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P = 0.019) and clarithromycin (90.1% vs. 64.2%, P = 0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P = 0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy.

Reversal of sleep apnea in uremia by dialysis.

Obstructive sleep apnea (OSA) is a common syndrome occurring in 1% to 4% of the population. While obesity is the most common predisposition to OSA, metabolic disorders have been associated with this syndrome. We describe a patient who presented with severe OSA while in an advanced untreated uremic state, which resolved following intensive dialysis. We speculate that the sleep disturbances, which are common in uremia, may be accounted for in some patients by OSA and may resolve with specific therapy for advanced renal failure.

Nonresolving pneumonia in steroid-treated patients with obstructive lung disease.

PURPOSE: To review autopsy-proven cases of opportunistic pneumonia and determine how many of these patients had received corticosteroid therapy for obstructive lung disease in order to define whether this therapy was the major risk factor predisposing to infection. PATIENTS AND METHODS: All autopsies performed at Winthrop-University Hospital over a 5-year period were reviewed, and 30 cases of opportunistic pneumonia were identified. In eight of 30 cases, corticosteroid therapy for chronic obstructive pulmonary disease (COPD) was the only identifiable risk factor for opportunistic infection. The other 22 patients had other well-defined risk factors for infection. Chart review of the eight patients with COPD was undertaken to define the clinical features of their infections. RESULTS: All eight patients had a progressive multilobar pneumonia that failed to resolve, either clinically or radiographically, despite the use of multiple broad-spectrum antibiotics. In four cases, the infection was community-acquired, while in the other four cases, it was nosocomial in origin. Despite the presence of a nonresolving pneumonia, opportunistic infection was generally not considered as a diagnostic possibility, with only one case being correctly diagnosed antemortem. Autopsy examination documented Aspergillus species as being responsible for six episodes of pneumonia, Candida albicans accounting for one episode, and cytomegalovirus accounting for one episode. CONCLUSION: Based on this experience, it is clear that corticosteroid therapy of COPD can lead to opportunistic pulmonary infection, in or out of the hospital. This diagnosis should be considered when patients receiving this therapy develop a pneumonia that fails to respond to broad-spectrum antibiotics.

Tension ball valve mucus plug in asthma.

This report describes a patient with status asthmaticus and respiratory failure in whom profound hypoxemia developed during mechanical ventilation. During the hypoxemic episode, breath sounds were absent over the left lung, and chest radiography revealed a hyperlucent left hemithorax with tension shift of the mediastinum to the right. The presence of lung markings in the left lung on radiography eliminated the possibility of tension pneumothorax and led to the diagnosis of tension mediastinal shift secondary to a ball valve obstruction by a central mucus plug. Bronchoscopic lung lavage removed the mucus plug, thereby correcting the hypoxemia. Recognition of this previously undescribed acute complication of mechanical ventilation in status asthmaticus is essential so that confusion with tension pneumothorax is avoided and appropriate therapy instituted.

Community-acquired pneumonia: a North American perspective.

The North American guidelines for pneumonia generally show agreement in both the Canadian and American approaches. However, much new data have appeared since the original recommendations, and revisions are needed. The general approach to empiric therapy that has been proposed in both the Canadian and American Thoracic Society documents does appear to be valid, and future recommendations will probably use the original approach as a framework for a more refined approach.

The role of bacteria in exacerbations of COPD. A constructive view.

The role of infection in exacerbations of COPD remains controversial and incompletely understood. Although some investigators believe that bacteria are not important for patients with exacerbation, we disagree and believe that patients with at least two of the three cardinal symptoms of exacerbation should receive antibiotic therapy. With an open-minded view of the area, we review the data, showing that bacteriologic studies, pathologic investigations, and clinical trials all support roles for bacteria and antibiotic therapy in this disease. Still, many questions remain, and future studies will be needed to better define the mechanisms of bacterial invasion in the bronchitic patient and to develop effective vaccines to prevent exacerbations. In the meantime, we must rely on antibiotic therapy, and we will need prospective studies to corroborate preliminary findings showing that different patients may require different therapies; thus, patient subsetting may be vital in the selection of antibiotic therapy for exacerbations of COPD.

Cost-effectiveness of gatifloxacin vs ceftriaxone with a macrolide for the treatment of community-acquired pneumonia.

STUDY OBJECTIVE: To determine the cost-effectiveness of sequential IV to oral gatifloxacin therapy vs IV ceftriaxone with or without IV erythromycin to oral clarithromycin therapy to treat community-acquired pneumonia (CAP) patients requiring hospitalization. PATIENTS: Two hundred eighty-three patients enrolled in a randomized, double-blind, clinical trial were eligible for inclusion in the cost-effectiveness analysis. METHODS: Data collected included patient demographics, clinical and microbiological outcomes, length of stay (LOS), and antibiotic-related LOS (LOSAR). Costs evaluated include drug acquisition (level 1); plus costs of preparation, dispensing, and administration, treating adverse events, and clinical failures (level 2); plus hospital per diem costs (level 3). Robustness of economic findings was tested using sensitivity analyses. RESULTS: Two hundred three patients were clinically and economically evaluable (98 receiving gatifloxacin and 105 receiving ceftriaxone). IV erythromycin was administered to 35 patients in the ceftriaxone-treated group. Oral conversion was achieved in 98% of patients in each group. Clinical cure and microbiological eradication rates did not differ statistically (98% and 97% with gatifloxacin vs 92% and 92% with ceftriaxone, respectively). Overall, neither geometric mean LOS nor LOSAR differed significantly (4.2 days and 4.1 days with gatifloxacin vs 4.9 days and 4.9 days with ceftriaxone, respectively). Treatment failures in the ceftriaxone group contributed to a mean incremental increase in LOSAR of 1.09 days and increased mean cost per patient. The geometric mean costs per patient (level 3) were $5,109 for gatifloxacin and $6,164 for ceftriaxone (p = 0.011). The cost-effectiveness ratios (mean cost per expected success) were $5,236:1 and $7,047:1 for gatifloxacin and ceftriaxone, respectively. CONCLUSIONS: Gatifloxacin monotherapy for CAP patients requiring hospitalization is clinically effective and provides an economic advantage compared to the regimen of ceftriaxone with or without erythromycin IV with a switch to oral clarithromycin.

Neutrophil-endothelial cell interaction in critical illness.

Sepsis syndrome frequently results in endothelial injury in many organ systems. To evaluate neutrophil-pulmonary endothelial cell interaction in the sepsis syndrome, we studied 39 critically ill patients prospectively and 20 normal volunteers. Thirteen patients with sepsis (mean age, 71.4 years), 14 patients in an intensive care unit control group (mean age 65.4 years), and 12 patients admitted with acute myocardial infarction (mean age, 66.8 years) were evaluated. Blood samples were drawn from septic patients within 24 hours and from ICU and MI patients within 72 hours of admission. All sepsis patients were culture positive, 6 of 13 from the blood. Both renal failure and ARDS developed in 54 percent of septic patients. 51Cr-labelled neutrophils were prepared and added to bovine pulmonary endothelial cell monolayers with and without added phorbol myristate acetate. Endothelial cells with adherent PMA and nonadherent PMN's, were harvested and radioactivity in each fraction measured with a gamma scintillation counter. Baseline and maximally stimulated (PMA, 3.0 ng/ml) neutrophil adherence to endothelial cells were similar in all patients groups. However, in septic patients, PMA-stimulated PMN adherence was reduced at lower doses, most significantly in those who developed ARDS within 24 to 48 hours of admission (p less than 0.05). Seventy-one percent of patients who developed ARDS had reduced stimulated adherence (PMA 1.0 ng/ml) compared to 22 percent of critically ill patients who did not. We conclude that diminished adherence of neutrophils to endothelium in response to low-level PMA stimulation is significantly more common in patients with sepsis who develop ARDS. Our findings suggest that PMN-endothelial cell interaction is altered by the time sepsis is clinically recognized but before the development of ARDS. We speculate that the observed reduction in adherence of the PMN to endothelial cells may be a consequence of down-regulation by mediators generated in the inflammatory response to sepsis and/or the need for active participation of septic endothelium in this interaction.

Non-cardiogenic pulmonary edema after pericardial drainage for cardiac tamponade.

We report a patient who developed adult respiratory distress syndrome following relief of pericardial tamponade. Because of increasing recognition of pulmonary edema in this situation, we recommend gradual removal of pericardial fluid with hemodynamic monitoring to limit the massive fluid shifts which appear to herald this dire complication.

Utility of fiberoptic bronchoscopy in nonresolving pneumonia.

Although fiberoptic bronchoscopy (FOB) has been traditionally used to evaluate nonresolving pneumonia, its efficacy is unknown. We, therefore, reviewed FOB in 35 consecutive patients who had (1) a roentgenographic infiltrate, (2) cough, (3) either temperature greater than 38.1 degrees C, leukocytosis, sputum production, (4) symptoms present for at least ten days, and antibiotic therapy for at least one week. Known lung cancer and AIDS were excluded. Fiberoptic bronchoscopy was diagnostic in 86 percent (12/14) in whom a specific cause was found. No patient had endobronchial cancer. Two patients with nondiagnostic FOB and persistent systemic symptoms had open lung biopsy specimens showing Wegener's granulomatosis and bronchiolitis obliterans with organizing pneumonia (BOOP). Twenty-one patients with nondiagnostic FOB had no final diagnoses other than community-acquired pneumonia. We conclude that FOB is extremely useful in finding a specific diagnosis for a nonresolving pneumonia when a specific diagnosis can be made. Fiberoptic bronchoscopy was most likely to yield a specific diagnosis in nonsmoking patients with multilobar infiltrates of long duration and could have been avoided in older, smoking, or otherwise compromised patients with lobar or segmental infiltrates with no decrease in diagnostic yield in our series.

Angiotensin converting enzyme in bronchoalveolar lavage in ARDS.

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.