Uncomplicated Community-acquired Pneumonia Research Articles

A tool for assessing the feasibility of comparative effectiveness research

Background: Comparative effectiveness research (CER) provides actionable information for health care decision-making. Randomized clinical trials cannot provide the patients, time horizons, or practice settings needed for all required CER. The need for comparative assessments and the infeasibility of conducting randomized clinical trials in all relevant areas is leading researchers and policy makers to non-randomized, retrospective CER. Such studies are possible when rich data exist on large populations receiving alternative therapies that are used as-if interchangeably in clinical practice. This setting we call “empirical equipoise.” Objectives: This study sought to provide a method for the systematic identification of settings it in which it is empirical equipoise that offers promised non-randomized CER. Methods: We used a standardizing transformation of the propensity score called “preference” to assess pairs of common treatments for uncomplicated community-acquired pneumonia and new-onset heart failure in a population of low-income elderly people in Pennsylvania, for whom we had access to de-identified insurance records. Treatment pairs were considered suitable for CER if at least half of the dispensings of each treatment-pair member fell within a preference range of 30% to 70%. Results: Among 3889 community-acquired pneumonia patients, insurance claims histories were sufficiently similar in seven drug pairs to suggest that observational CER might be effective. Relapse appears to have been less common in levofloxacin recipients than in similar patients given other products. In 6035 heart failure patients, metoprolol, carvedilol, and atenolol were employed in patients with similar claims histories, and thus might be suitable for observational CER. The long-acting succinate formulation of metoprolol had lower failure rates in head-to-head comparisons with all other beta-blockers. Both findings are candidates for further investigation. Confounding by unmeasured factors operating in the same manner as the measured covariates would not have produced the apparent superiority of levofloxacin, which was given to people in poorer respiratory health. The baseline covariate distributions of persons starting beta-blockers suggest only that carvedilol recipients were healthier than others. Conclusion: A straightforward algorithm can identify empirical equipoise, in which prescribers as a group seem evenly divided on the merits of alternative therapies. This is the setting in which CER may be most necessary and is likely to be most accurate. The imbalances identified by propensity models can identify situations in which the results of screening analyses may be biased in the direction of the observed effect.

Do We Know When, What and For How Long to Treat?

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.

Impact of a Guideline on Management of Children Hospitalized With Community-Acquired Pneumonia

We sought to describe the impact a clinical practice guideline (CPG) had on antibiotic management of children hospitalized with community-acquired pneumonia (CAP). We conducted a retrospective study of discharged patients from a children's hospital with an ICD-9-CM code for pneumonia (480-486). Eligible patients were admitted from July 8, 2007, through July 9, 2009, 12 months before and after the CAP CPG was introduced. Three-stage least squares regression analyses were performed to examine hypothesized simultaneous relationships, including the impact of our institution\x{2019}s antimicrobial stewardship program (ASP). The final analysis included 1033 patients: 530 (51%) before the CPG (pre-CPG) and 503 (49%) after the CPG (post-CPG). Pre-CPG, ceftriaxone (72%) was the most commonly prescribed antibiotic, followed by ampicillin (13%). Post-CPG, the most common antibiotic was ampicillin (63%). The effect of the CPG was associated with a 34% increase in ampicillin use (P < .001). Discharge antibiotics also changed post-CPG, showing a significant increase in amoxicillin use (P < .001) and a significant decrease in cefdinir and amoxicillin/clavulanate (P < .001), with the combined effect of the CPG and ASP leading to 12% (P < 0.001) and 16% (P < .001) reduction, respectively. Overall, treatment failure was infrequent (1.5% vs 1%). A CPG and ASP led to the increase in use of ampicillin for children hospitalized with CAP. In addition, less broad-spectrum discharge antibiotics were used. Patient adverse outcomes were low, indicating that ampicillin is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP.

Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia

In order to evaluate the use of an algorithm based on a procalcitonin (PCT) cut-off value as a means of guiding antibiotic therapy, 319 hospitalised children with uncomplicated community-acquired pneumonia (CAP) were randomised 1:1 to be treated on the basis of the algorithm or in accordance with standard guidelines. The children in the PCT group did not receive antibiotics if their PCT level upon admission was <0.25 ng/mL, and those receiving antibiotics from the time of admission were treated until their PCT level was ≥ 0.25 ng/mL. The final analysis was based on 155 patients in the PCT group and 155 in the control group. In comparison with the controls, the PCT group received significantly fewer antibiotic prescriptions (85.8% vs 100%; p < 0.05), were exposed to antibiotics for a shorter time (5.37 vs 10.96 days; p < 0.05), and experienced fewer antibiotic-related adverse events (3.9% vs 25.2%; p < 0.05), regardless of CAP severity. There was no significant between-group difference in recurrence of respiratory symptoms and new antibiotic prescription in the month following enrollment. The results of this first prospective study using a PCT cut-off value to guide antibiotic therapy for pediatric CAP showed that this approach can significantly reduce antibiotic use and antibiotic-related adverse events in children with uncomplicated disease. However, because the study included mainly children with mild to moderate CAP and the risk of the use of the algorithm-based approach was not validated in a relevant number of severe cases, further studies are needed before it can be used in routine clinical practice.

Dexamethasone Shortens Hospitalization in Uncomplicated Community-Acquired Pneumonia

Some of the considerable morbidity and mortality associated with community-acquired pneumonia (CAP) probably results from organ damage caused by

Retrospective survey for sialidase activity in Mycoplasma pneumoniae isolates from cases of community-acquired pneumonia

BackgroundSialidase is a well-known virulence factor of other respiratory pathogens, but was only recently documented to occur in some species of Mycoplasma. The sialidase activity expressed can vary quantitatively among strains within a species of mycoplasma, from undetectable to amounts that correlate positively with strain virulence. Very few isolates of Mycoplasma pneumoniae had ever been examined for sialidase activity, so it was unknown whether sialidase may contribute to diseases involving this species.FindingsNo sialidase activity was detected by spectrofluorometric assay of 15 laboratory strains and 91 clinical isolates of M. pneumoniae banked over many years from patients having radiologically-confirmed, uncomplicated community-acquired pneumonia.ConclusionsThe annotated genome of strain M129 (GenBank NC_000912, ATCC 29342), also isolated from a patient with pneumonia, accurately represents the absence of sialidase genes from strains of M. pneumoniae typically associated with uncomplicated community-acquired pneumonia. A possible involvement of sialidase in neurologic or other extra-respiratory manifestations of M. pneumoniae mycoplasmosis remains to be investigated.

Variability in Pediatric Infectious Disease Consultants' Recommendations for Management of Community-Acquired Pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is a common childhood infection. CAP complications, such as parapneumonic empyema (PPE), are increasing and are frequently caused by antibiotic-resistant organisms. No clinical guidelines currently exist for management of pediatric CAP and no published data exist about variations in antibiotic prescribing patterns. Our objectives were to describe variation in CAP clinical management for hospitalized children by pediatric infectious disease consultants and to examine associations between recommended antibiotic regimens and local antibiotic resistance levels.MethodsWe surveyed pediatric members of the Emerging Infections Network, which consists of 259 pediatric infectious disease physicians. Participants responded regarding their recommended empiric antibiotic regimens for hospitalized children with CAP with and without PPE and their recommendations for duration of therapy. Participants also provided information about the prevalence of penicillin non-susceptible S. pneumoniae and methicillin-resistant S. aureus (MRSA) in their community.ResultsWe received 148 responses (57%). For uncomplicated CAP, respondents were divided between recommending beta-lactams alone (55%) versus beta-lactams in combination with another class (40%). For PPE, most recommended a combination of a beta-lactam plus an anti-MRSA agent, however, they were divided between clindamycin (44%) and vancomycin (57%). The relationship between reported antibiotic resistance and empiric regimen was mixed. We found no relationship between aminopenicillin use and prevalence of penicillin non-suscepetible S. pneumoniae or clindamycin use and clindamycin resistance, however, respondents were more likely to recommend an anti-MRSA agent when MRSA prevalence increased.ConclusionsSubstantial variability exists in recommendations for CAP management. Development of clinical guidelines via antimicrobial stewardship programs and dissemination of data about local antibiotic resistance patterns represent opportunities to improve care.

Character features of community-acquired pneumonia during the pandemic influenza A / N1N1 / 2009

Summary. Course and complications of community-acquired pneumonia (CAP) during the pandemic influenza A / N1N1 / 2009 were studied based on clinical, laboratory and radiology data. The study involved 250 patients, of them 57 patients with uncomplicated CAP (the 1st group), 124 patients with CAP and the systemic inflammatory response syndrome (SIRS) (the 2nd group), 53 patients with CAP and severe sepsis (the 3rd group), and 16 patients with CAP and septic shock (the 4th group). All patients received antiviral, antibacterial and symptomatic therapy; 193 (77.2 %) patients needed supplemental oxygen, 108 (56 %) were admitted to ICU, 15.6 % of patients needed mechanical ventilation. Bilateral lung injury was diagnosed in 225 patients (90.0 %). Overall mortality was 10.4 %, mortality in obese patients was 30.0 %.

Measuring Acceptable Treatment Failure Rates for Community-Acquired Pneumonia: Potential for Reducing Duration of Treatment and Antimicrobial Resistance

This study was designed to establish the rates of treatment failure for community-acquired pneumonia that are acceptable to knowledgeable and experienced physicians, in order to facilitate the interpretation of existing studies and the design of new studies aimed at optimizing the duration of antibiotic therapy. Reducing the duration of antibiotic therapy is one strategy for reducing antibiotic exposure and thereby minimizing the potential for the emergence of antimicrobial resistance. Survey soliciting the acceptable failure rate for treatment given to an adult patient with uncomplicated community-acquired pneumonia treated with standard-of-care therapy in the outpatient setting. Analysis was performed using a modification of established methods of contingent valuation analysis. Six hundred eighty infectious diseases physicians in North America who were also members of the Emerging Infections Network of the Infectious Diseases Society of America. Three hundred seventy-five (55.1%) of 680 physicians responded to the survey. The median acceptable failure rate for treatment was 13.5%. Five hundred ten respondents (75.0%) found a failure rate of 7.3% acceptable, and 170 respondents (25.0%) found a failure rate of 19.8% acceptable. This study identified the failure rates for treatment of community-acquired pneumonia that were acceptable to infectious disease physicians. This range of acceptable treatment failure rates may facilitate the design of studies aimed at optimizing the duration of antimicrobial therapy for community-acquired pneumonia.

Development of parapneumonic empyema in children

The aim of the study was to find clinical predictors for parapneumonic empyema in children. Thirty-seven children treated for parapneumonic empyema at the Department of Pediatrics, Turku University Hospital, were retrospectively evaluated. Two distinct comparison groups of children with uncomplicated community-acquired pneumonia with alveolar consolidation (n = 37 in both groups) were included. Clinical and laboratory data on admission as well as fever kinetics and inflammatory markers during hospitalization were analyzed. In a multivariate analysis, a history of prolonged fever, tachypnoea and pain on abdominal palpation on admission were the most significant clinical predictors for empyema. On admission, serum C-reactive protein levels were higher among children with empyema than among those with uncomplicated pneumonia (means, 234 mg/L vs. 178 mg/L; p = 0.037). During hospitalization, prolonged fever and persistence of high serum C-reactive protein levels were associated with empyema. At the initial evaluation, pleural fluid was not reported in 35% of children with empyema. Early recognition of developing empyema is challenging. Children with pneumonia presenting with prolonged fever, tachypnoea, pain on abdominal palpation and high serum C-reactive protein levels are at risk for parapneumonic empyema.

Purpura-Producing Streptococcus pneumoniae

Clinical manifestations of purpura-producing Streptococcus pneumoniae may mimic meningococcemia. The pathogenesis of S. pneumoniae purpura has been elucidated, but clinical cases of benign purpura due to this organism are rare. We report the first case of purpura-producing S. pneumoniae occurring in the setting of uncomplicated community-acquired pneumonia in an immunocompetent adult.

The Contribution of Blood Cultures to the Clinical Management of Adult Patients Admitted to the Hospital With Community-Acquired Pneumonia: A Prospective Observational Study

To assess the clinical usefulness of blood cultures (BCs) in the management of patients hospitalized with community-acquired pneumonia (CAP). A prospective, observational study to investigate the contribution of BCs to the management and outcomes of adult patients presenting with CAP. Nineteen Canadian hospitals. Adults admitted to the hospital with CAP between January 1, 1998, and July 31, 1998. The courses of therapy in patients for whom BC results yielded organisms considered to be clinically significant were analyzed to determine whether the BCs had contributed to management or outcome. Forty-three of 760 patients had significantly positive BC results. Patients with CAP who had BCs performed had a 1.97% chance (15 of 760 patients) of having a change of therapy directed by BC results. Patients in whom BCs yielded positive results had a 34.8% chance (15 of 43 patients) of having a change in therapy determined by BC results, and had a 58.1% chance (25 of 43 patients) of having a course of therapy contraindicated by BC results. Severity of illness, as measured by the pneumonia severity index, correlated poorly with the yield of BCs. BC results were positive in 8.0% of patients in risk classes I and II, 6.2% of patients in risk class III, 4.6% of patients in risk class IV, and 5.2% of patients in risk class V. BCs have limited usefulness in the routine management of patients admitted to the hospital with uncomplicated CAP.

Linezolid: a review of its use in the management of serious gram-positive infections.

Linezolid is the first of a new class of antibacterial drugs, the oxazolidinones. It has inhibitory activity against a broad range of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate S. aureus (GISA), vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae. The drug also shows activity against certain anaerobes, including Clostridium perfringens, C. difficile, Peptostreptococcus spp. and Bacteroidesfragilis. In controlled phase III studies, linezolid was as effective as vancomycin in the treatment of patients with infections caused by methicillin-resistant staphylococci and also demonstrated efficacy against infections caused by VRE. Further phase III studies have demonstrated that linezolid is an effective treatment for patients with nosocomial pneumonia, for hospitalised patients with community-acquired pneumonia, and for patients with complicated skin or soft tissue infections (SSTIs). In these studies, linezolid was as effective as established treatments, including third-generation cephalosporins in patients with pneumonia, and oxacillin in patients with complicated SSTIs. Oral linezolid 400 or 600mg twice daily was as effective as clarithromycin 250mg twice daily or cefpodoxime proxetil 200mg twice daily in the treatment of patients with uncomplicated SSTIs or community-acquired pneumonia. Linezolid is a generally well tolerated drug. The most frequently reported adverse events in linezolid recipients were diarrhoea, headache, nausea and vomiting. Thrombocytopenia was also documented in a small proportion (about 2%) of patients treated with the drug. Linezolid has good activity against gram-positive bacteria, particularly multidrug resistant strains of S. aureus (including GISA), Enterococcus faecium and E. faecalis (including VRE). In controlled clinical trials, linezolid was as effective as vancomycin in eradicating infections caused by methicillin-resistant Staphylococcus spp. and has demonstrated efficacy against infections caused by VRE. As the level of resistance to vancomycin increases among S. aureus and enterococci, linezolid is poised to play an important role in the management of serious gram-positive infections.

The Effects of Erythromycin on the Electrocardiogram

Various cardiac electrophysiologic effects have been attributed to erythromycin. During the course of treating a pneumonia patient with IV erythromycin, the conversion of atrial fibrillation to a sinus rhythm, and its subsequent reversal, appeared to be causally related to the introduction and cessation of this antibiotic. This observation suggested the need for studying the changes in the ECG following the use of IV erythromycin in a typical clinical setting. A prospective comparative drug study. A university-affiliated teaching hospital. Nineteen patients being treated for uncomplicated community-acquired pneumonia. IV erythromycin, 500 mg, and/or IV cefuroxime, 750 mg, infused in 250 mL of saline over 20 min. In the 11 patients who were receiving both of the antibiotics, cefuroxime was administered immediately before erythromycin was infused. The 12-lead ECG measurements were obtained before infusion, at 5-min intervals during each infusion, and at 5 and 10 min after the infusions had been completed. All of the ECG complexes and intervals were measured using a software program (Interpretive Cardiograph; Hewlett Packard; Palo Alto, CA). The administration of IV erythromycin increased heart rate and prolonged the corrected QT (QTc) interval. These changes were significant at 15 min of the infusion, and were no longer evident 5 min after the infusion had been stopped. The administration of IV cefuroxime did not produce any ECG changes. A single, standard dose of IV erythromycin prolongs the QTc interval; therefore, the drug should always be administered as a slow infusion. ECG monitoring should accompany erythromycin therapy in critically ill patients, in patients with electrolyte disorders, or in patients taking other drugs with similar cardiac effects.

Comparison of cefotaxime with ceftriaxone given intramuscularly 12-hourly for community-acquired pneumonia

Cefotaxime 1 g intramuscularly (i.m.) 12-hourly was compared with ceftriaxone 1 g i.m. 12-hourly in adult patients requiring hospitalization with uncomplicated community-acquired pneumonia. Fifty-two patients were enrolled and two were subsequently withdrawn, leaving 50 patients who completed the study; 23 received cefotaxime and 27 received ceftriaxone. Clinical cure was achieved in 49 of the 50 patients (98%). One treatment failure occurred in a patient who received ceftriaxone. The only significant pathogen isolated from the pretreatment sputum cultures was Streptococcus pneumoniae (50%). All isolates were sensitive to both drugs. Cefotaxime 1 g i.m. 12-hourly was as effective as ceftriaxone in the treatment of patients with uncomplicated community-acquired pneumonia requiring hospital admission.

Community-acquired pneumonia

Quantitative and qualitative elastase inhibitory capacity (EIC) alpha 1 proteinase inhibitor (alpha 1 PI) was measured in pulmonary arterial and systemic arterial blood of patients with community-acquired pneumonia (CAP). Eleven patients with uncomplicated CAP were compared with 16 patients with fulminating pneumonia requiring intensive care management. An appropriate increase in quantitative alpha 1 PI was demonstrated in all patients. A significant functional inactivation of alpha 1 PI was demonstrated in the ICU-treated patients that was not apparent in the uncomplicated CAP patients (p less than .01). This low EIC returned to normal 4 wk after hospital discharge in all survivors. A significant (p less than .02) difference in EIC between the pulmonary arterial and systemic arterial blood was found in the nonsurvivors on admission, which suggests that alpha 1 PI is inactivated in the lungs of patients with fulminating CAP. The present data demonstrate that alpha 1 PI is functionally inactivated in patients with fulminating CAP. This low serum functional alpha 1 PI may result in proteolytic lung damage and an unfavorable outcome.