Antibiotics For Community-acquired Pneumonia Research Articles

A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease

The demographics and comorbidities of patients with community acquired pneumonia (CAP) vary enormously but stratified treatment is difficult because aetiological studies have failed to comprehensively identify the pathogens. Our aim was to describe the bacterial microbiota of CAP and relate these to clinical characteristics in order to inform future trials of treatment stratified by co-morbidity. CAP patients were prospectively recruited at two UK hospitals. We used 16S rRNA gene sequencing to identify the dominant bacteria in sputum and compositional data analysis to determine associations with patient characteristics. We analysed sputum samples from 77 patients and found a Streptococcus sp. and a Haemophilus sp. were the most relatively abundant pathogens. The Haemophilus sp. was more likely to be dominant in patients with pre-existing lung disease, and its relative abundance was associated with qPCR levels of Haemophilus influenzae. The most abundant Streptococcus sp. was associated with qPCR levels of Streptococcus pneumoniae but dominance could not be predicted from clinical characteristics. These data suggest chronic lung disease influences the microbiota of sputum in patients with CAP. This finding could inform a trial of stratifying empirical CAP antibiotics to target Haemophilus spp. in addition to Streptococcus spp. in those with chronic lung disease.

1466. Adherence to Empiric Treatment Recommended by IDSA/PIDS Pediatric Community-Acquired Pneumonia (CAP) Guidelines According to Immunization Status

BackgroundCurrent pediatric CAP guidelines recommend empiric antibiotic treatment based on patient’s immunization status against Haemophilus influenzae and Streptococcus pneumoniae. The primary objective of this study was to assess the current empiric antimicrobial treatment practices for CAP based on the immunization status of pediatric patients.MethodsThis retrospective cohort included pediatric patients diagnosed with CAP and received initial empiric antibiotics after presenting to the institution. The cohorts were categorized as fully immunized or not fully immunized consistent with state immunization health records and national recommendations according to the child’s age. The primary outcome was receipt of appropriate vs. inappropriate antibiotics according to guideline recommendations. Multivariable analyses were used to evaluate inappropriate empiric antibiotics for CAP with immunizations status as exposure of interest. Secondary outcomes included length of stay and 30-day readmission rates.ResultsA total of 189 patients (129 fully immunized and 60 not fully-immunized) were included in the interim analysis. A total of 104 patients (55%) received inappropriate antibiotics [62 of the fully immunized (48%) and 42 of the not fully immunized (70%) received inappropriate antibiotics (P = 0.0048)]. Multivariable analysis identified not fully-immunized and age as independent predictors for inappropriate empiric antibiotics for CAP, aOR 2.77, 95% CI (1.20, 5.89), P = 0.008, and aOR 1.41, 95% CI (1.15, 1.72), P = 0.001; respectively. In terms of secondary outcomes, not fully-immunized patients had longer length of stay, higher readmission in 30 days, and greater need for oxygen supplementation, but none of these results were statistically significant.ConclusionCurrently, the majority of pediatric patients treated for CAP received inappropriate empiric antibiotics. Not fully-immunized patients were more likely to receive inappropriate empiric antibiotics for CAP and subsequently did not have improved morbidity.Disclosures All authors: No reported disclosures.

Short-course versus long-course therapy of the same antibiotic for community-acquired pneumonia in adolescent and adult outpatients.

Community-acquired pneumonia (CAP) is a lung infection that can be acquired during day-to-day activities in the community (not while receiving care in a hospital). Community-acquired pneumonia poses a significant public health burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses for CAP may limit treatment costs and adverse effects, but the optimal duration of antibiotic treatment is uncertain. To evaluate the efficacy and safety of short-course versus longer-course treatment with the same antibiotic at the same daily dosage for CAP in non-hospitalised adolescents and adults (outpatients). We planned to investigate non-inferiority of short-course versus longer-term course treatment for efficacy outcomes, and superiority of short-course treatment for safety outcomes. We searched CENTRAL, which contains the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, five other databases, and three trials registers on 28 September 2017 together with conference proceedings, reference checking, and contact with experts and pharmaceutical companies. Randomised controlled trials (RCTs) comparing short- and long-courses of the same antibiotic for CAP in adolescent and adult outpatients. We planned to use standard Cochrane methods. Our searches identified 5260 records. We did not identify any RCTs that compared short- and longer-courses of the same antibiotic for the treatment of adolescents and adult outpatients with CAP.We excluded two RCTs that compared short courses (five compared to seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) not commonly used in practice for the treatment of CAP. In particular, gemifloxacin is no longer approved for the treatment of mild-to-moderate CAP due to its questionable risk-benefit balance, and reported adverse effects. Moreover, the safety profile of telithromycin is also cause for concern.We found one ongoing study that we will assess for inclusion in future updates of the review. We found no eligible RCTs that studied a short-course of antibiotic compared to a longer-course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.

Antibiotic treatment in childhood community-acquired pneumonia - clinical practice versus guidelines: results from two university hospitals.

Background and aimsCommunity-acquired pneumonia (CAP) is a both common and serious childhood infection. Antibiotic treatment guidelines help to reduce inadequate antibiotics prescriptions.MethodsWe conducted a retrospective study at the Clinical Emergency Hospital for Children, 3rd Pediatric Clinic, Cluj-Napoca and Dr. Gavril Curteanu Clinical City Hospital, in Oradea. All patients discharged with a diagnosis of CAP between December 1, 2014 and February 28, 2015, were included in the study.ResultsThere were 146 cases discharged with pneumonia in Cluj-Napoca center (mean age 4 years; range: 1 month – 16 years), and 212 cases in Oradea center (mean age 0.9 years; range: 2 weeks – 8 years). All cases were analyzed. The analysis made in Clinical Emergency Hospital for Children, 3rd Pediatric Clinic, Cluj-Napoca, showed that the antibiotics used in children hospitalized with community-acquired CAP are cefuroxime (43%), ceftriaxone (23%), macrolides (16%), ampicillin in association with an aminoglycoside (6%) and other antibiotics. The same antibiotics were used in Dr. Gavril Curteanu Clinical City Hospital of Oradea, where ampicillin in association with aminoglycoside was utilized in younger children (mean age 1.3 years), while ceftriaxone in older children (5.7 years) and children with high inflammation markers (ESR, CRP). From 11 pleurisy cases, 9 received cefuroxime or ceftriaxone.ConclusionsThere was a wide variability in CAP antibiotic treatment across university hospitals, regarding antibiotic choice and dosing. Antibiotic selection was not always related to the clinical and laboratory characteristics of the patient. The national guideline was not followed, especially in children aged one to three months.

Ketolide antibiotics: will they ever be used for community-acquired pneumonia?

There is no perfect antibiotic for community-acquired pneumonia (CAP). β-lactams do not cover atypical organisms, most importantly, Legionella . Fluoroquinolones remain active against Streptococcus pneumoniae and cover atypical bacteria, but are associated with serious side effects including tendon rupture and a variety of neurologic side effects.

Potential Impact of the DRIP Score on Antibiotic Use: a Retrospective Single-Center Study

BackgroundThe Drug Resistance in Pneumonia score (DRIP) is a recently developed prediction tool to identify patients with community-acquired pneumonia (CAP) at increased risk for drug resistant pathogens (DRP). The DRIP score has better performance characteristics than other available prediction tools which have been associated with increased broad-spectrum antibiotic use. We evaluated the potential impact of the DRIP score on CAP management at the Salt Lake City VA, a 106 bed facility with a Hospitalist service staffed by Internal Medicine residents and Department of Medicine faculty and an antibiotic stewardship program (ASP).MethodsWe performed a retrospective chart review of adult inpatients with pneumonia present on admission based on ICD9/10 coding between February 2016 and April 2017. Both DRIP and HCAP scores were calculated for each patient and antibiotic selection was collected by manual chart review. We compared actual antibiotic selection with potential changes in broad-spectrum antibiotic use in all patients and patients with a DRIP score ≥4, the cutoff where broad-spectrum antibiotic use is suggested. Microbiology results, mortality, and 30-day readmission were also collected.ResultsWe identified 184 patients during the study period. Respiratory cultures were obtained in 27% (50/184) of participants with 2% (3/184) positive for a CAP-DRp. 7% (12/169) were positive for MRSA colonization upon admission. 24% (45/184) had DRIP ≥4 as compared with 47% (87/184) meeting HCAP criteria. 158 were treated for bacterial pneumonia of which 85% (134/158) received CAP antibiotics. Strict DRIP adherence upon admission would have led to 13% (21/158) more patients on broad-spectrum antibiotics. In the subset of patients with a DRIP score ≥4, DRIP adherence would have led to 65% (26/40) more patients on broad-spectrum antibiotics. 30-day mortality (9%) and readmission (15%) rates were comparable with Centers for Medicare Services (CMS) statistics.ConclusionIn the setting of robust ASP efforts and low rates of DRPs, the DRIP score may lead to increased use of broad-spectrum antibiotics. The impact of the DRIP score on antibiotic use and clinical outcomes warrants further large-scale evaluation in a variety of settings.Disclosures All authors: No reported disclosures.

Antibiotic Resistance in Community-Acquired Pneumonia Pathogens.

The overwhelming majority of cases of community-acquired pneumonia (CAP) can be treated with the standard antibiotic regimens of a macrolide and cephalosporin or a fluoroquinolone. Despite high rates, current levels of β-lactam resistance generally do not result in treatment failure for patients with CAP when appropriate agents and doses are used. Following the introduction of the pneumococcal conjugate vaccines, the incidence of invasive pneumococcal disease declined drastically, coinciding with a decrease in penicillin resistance. Risk factors for methicillin-resistant S. aureus follow two patterns: (1) healthcare-associated risk factors and (2) pneumonia from exotoxin-producing community-acquired strains. The latter is associated with need for antibiotics which inhibit protein synthesis for optimal management. Since 2000, macrolide-resistance in M. pneumoniae has rapidly emerged worldwide, especially in Asian countries. The inability to routinely culture H. influenzae suggests that macrolide and β-lactam resistance, while present, is not a big issue. Unless risk factors for a hospital-associated strain are present, the most common Enterobacteriaceae to cause CAP, including Escherichia coli and Klebsiella, are generally susceptible to usual CAP antibiotics. Given the limited role of antibiotic resistance in CAP, a strong rationale is needed for use of antibiotics other than the standard β-lactam/macrolide or fluoroquinolone regimens.

A Rare Case of Idiopathic Interstitial Pneumonia With Good Outcome: Acute Fibrinous and Organizing Pneumonia

SESSION TITLE: Global Case Report Poster - Miscellaneous SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare form of idiopathic interstitial pneumonia (IIP), which is now increasingly more recognized and has recently been added to the American Thoracic Society/European Respiratory Society international multidisciplinary classification of IIP. It is still regarded as a rare histologic pattern and is not yet classified as a new separate IIP entity. [1] Questions remain whether it is merely a histologic variant of existing IIPs or occurs in relation to other diseases such as hypersensitivity pneumonia or connective tissue disorder. It may also represent a histologic pattern that occurs in the clinical spectrum of diffuse alveolar damage and organizing pneumonia, and may reflect a tissue sampling issue. We report our experience with a case of AFOP treated successfully with corticosteroid and mycophenolate mofetil. CASE PRESENTATION: A 65-year-old Caucasian male, retired school teacher with no significant past medical history presented with progressive dyspnea and dry cough over 2 weeks. He had a 20-pack-year history of smoking, but quit 20 years ago. Regular medications included fish oil and glucosamine for knee osteoarthritis. There is no family history of similar presentation or connective tissue disorders. He was born in Australia and currently lived in a regional area, but with no exposure to farm animals. He had 1 pet dog. Hobbies included woodwork and gardening with regular exposure to mulch hay and potting mix. There were no sick contacts otherwise. There was no sputum production, hemoptysis, fever, night sweats or flu-like illness. He did have intentional weight loss of 6 kilograms over the last 3 months. There were no myalgia, arthralgia, sicca symptoms, abdominal or urinary symptoms. The only pertinent clinical finding was bilateral inspiratory crepitations without accompanying signs of overt heart failure. Initial chest x-ray demonstrated widespread interstitial and alveolar opacities. There was mild leukocytosis with neutrophilia. Interestingly, there was also a transient mild borderline eosinophilia. Urinalysis, renal and liver functions were unremarkable. Antibiotics for community-acquired pneumonia and diuretic therapies resulted in no improvement. A computed tomography pulmonary angiogram (CTPA) showed no pulmonary embolus. However, significant homogeneous bilateral ground-glass opacities and non-specific sub-pleural nodular infiltrates were demonstrated. There were no consolidation or significant lymphadenopathies. Bronchoscopy with transbronchial biopsy revealed no endobronchial abnormalities. Biopsies showed alveolar space filling by fibrin and macrophages, hyperplastic pneumocytes and mildly expanded interstitium with mild chronic inflammatory infiltrates. There were no granuloma, hyaline membrane, oesinophils, inclusion bodies, fibrosis or malignancy. All bacterial, mycobacterial and fungal cultures were negative. Viral PCRs were also negative. Infectious, hypersensitivity and autoimmune serologies were insignificant. A diagnosis of AFOP was made and the patient was commenced on Methylprednisolone followed by long-term prednisolone and additional Mycophenolate mofetil therapy for 6 months. Follow-up for the last 10 months showed complete radiological resolution with normalization and stability of diffusing capacity for carbon monoxide and 6-minute walk test. DISCUSSION: The classification of AFOP as a separate disease entity is still unclear, as it may belong to a spectrum of other interstitial pneumonias. Our experience posed a similar diagnostic challenge. There were risk factors and radiological evidence for hypersensitivity pneumonia, but histological and serological evidence were lacking. There has been a similar case report in which combined corticosteroid and mycophenolate therapy proved successful. [2] Our patient also received a similar therapy with success. CONCLUSIONS: AFOP is a rare form of idiopathic interstitial pneumonia. Combined corticosteroid and mycophenolate therapy may be effective in its treatment. Reference #1: Travis WD, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013 Sep 15;188(6):733-48. Reference #2: Bhatti S, et al. Severe acute fibrinous and organizing pneumonia (AFOP) causing ventilatory failure: successful treatment with mycophenolate mofetil and corticosteroids. Respir Med. 2009 Nov;103(11):1764-7. DISCLOSURE: The following authors have nothing to disclose: Anuk Kruavit, Rebecca Pearson, Subash Heraganahally No Product/Research Disclosure Information

Prescription of antibiotics in community-acquired pneumonia in children: are we following the recommendations?

ObjectiveTo assess the adequacy of antibiotic prescription in children hospitalized for pneumonia in a reference pediatric hospital in Brazil.MethodsThis was a cross-sectional study involving children aged between 1 month and 5 years who were hospitalized between October 2010 and September 2013. The classification of community-acquired pneumonia (CAP) was based on the clinical and radiological criteria of the World Health Organization (WHO). The analysis of antibiotic adequacy was performed according to the main guidelines on CAP treatment, which include the WHO guidelines, Brazilian Society of Pediatrics guidelines, and international guidelines (Pediatrics Infectious Diseases Society, the Infectious Disease Society of America, British Thoracic Society, and Consenso de la Sociedad latinoamericana de Infectología). A multivariate analysis was performed including variables that have statistical significance of P≤0.25 in the bivariate analysis.ResultsThe majority of the 452 hospitalized children were classified as having severe or very severe CAP (85.18%), and inadequate empiric antimicrobial therapy was started in 26.10% (118/452) of them. Ampicillin was the most used empiric antibiotic therapy (62.17%) for pneumonia, followed by a combination of ampicillin and associated with gentamicin. The initially proposed regimen was modified in 29.6% of the patients, and the most frequent change was the replacement of ampicillin by oxacillin combined with chloramphenicol. The median hospitalization time was 8.5 days, and the lethality rate was 1.55%. There was no statistical difference in adequacy in relation to the severity of pneumonia or degree of malnutrition. In the bivariate analysis, inadequacy of antibiotic therapy regimen was higher in patients undergoing oxygen therapy (P<0.05), which was given to 219 patients (48.45%). Pleural effusion was observed in 118 patients (26.11%) and was associated with higher prescription inadequacy, and it was the only factor that remained in the multivariate analysis (odds ratio =8.89; 95% confidence interval 5.20–15.01).ConclusionAdherence to the main guidelines for antimicrobial therapy according to the childhood CAP was unsatisfactory. Compliance with the guidelines is essential for both the management of pneumonia cases and the decrease in bacterial resistance and it is one of the cornerstone of WHO police of controlling antibiotic resistance.

Antibiotics for Community-Acquired Pneumonia in Adults.

Antibiotics for Community-Acquired Pneumonia in Adults.

Antibiotics for Community-Acquired Pneumonia in Adults.

Antibiotics for Community-Acquired Pneumonia in Adults.

Update on the combination effect of macrolide antibiotics in community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a leading cause of death from an infectious cause worldwide. Guideline-concordant antibiotic therapy initiated in a timely manner is associated with improved treatment responses and patient outcomes. In the post-antibiotic era, much of the morbidity and mortality of CAP is as a result of the interaction between bacterial virulence factors and host immune responses. In patients with severe CAP, or who are critically ill, there is a lot of emerging observational evidence demonstrating improved survival rates when treatment using combination therapy with a β-lactam and a macrolide is initiated, as compared to other antibiotic regimes without a macrolide. Macrolides in combination with a β-lactam antibiotic provide broader coverage for the atypical organisms implicated in CAP, and may contribute to antibacterial synergism. However, it has been postulated that the documented immunomodulatory effects of macrolides are the primary mechanism for improved patient outcomes through attenuation of bacterial virulence factors and host systemic inflammatory responses. Despite concerns regarding the limitations of observational evidence and the lack of confirmatory randomized controlled trials, the potential magnitude of mortality benefits estimated at 20-50% cannot be overlooked. In light of recent data from a number of trials showing that combination treatment with a macrolide and a suitable second agent is justified in all patients with severe CAP, such treatment should be obligatory for those admitted to an intensive care setting.

Prescribing pattern of antibiotics in community-acquired pneumonia in a teaching hospital of Southeast Asia

Objective: To study and describe the antibiotic prescribing habits of physicians for 117 patients with community-acquired pneumonia (CAP). Materials and Methods: A medicine consultant or a pulmonologist supervised and treated 45 (38%) patients. Out of 45 patients, 7 (16%) were given macrolide, 12 (26%) received beta-lactam antibiotics, 14 (31%) were given a combination of beta-lactam and macrolide, and 12 (26%) were given a combination of more than one antibiotics. Seventy-two (62%) patients were seen by other specialists, of whom 5 (6%) were given macrolide, 35 (48%) were given beta-lactam, 4 (6%) were administered a combination of beta-lactam and macrolide, 2 (3%) received quinolones, and 26 (36%) patients received various combinations. In 47 out of 117 patients, therapy was modified, which included 12 patients who underwent step-down switch. The duration of hospitalization was 26 days for those patients whose therapy was modified. Patients who underwent step-down switch had a hospital stay of 7 days, whereas those who did not have any modification in the treatment stayed for 10 days in the hospital. Results: Beta-lactam antibiotic was more commonly used, at least 3.8 times more than a macrolide. Other combinations of antibiotics were given in 28%, 68%, and 44% of patients treated by a medicine specialist, pulmonologist, and other specialties, respectively. Conclusion: These data demonstrate that in spite of the advances of knowledge in the management of CAP, there exists variability in the prescribing habits of the attending physician.

Poor compliance with community-acquired pneumonia antibiotic guidelines in a large Australian private hospital emergency department.

This study evaluated guideline concordance and time to administration of antibiotics in community-acquired pneumonia (CAP) in a private Australian emergency department (ED). Two key components in the management of CAP are timely administration and appropriate choice of antibiotic therapy. The use of antibiotics outside of guidelines can potentially increase rates of antibiotic resistance. Previous studies that evaluate guideline concordance have largely been conducted in Australian public hospitals; however, private hospitals comprise a significant portion of Australian health care. One hundred and thirty patients admitted to a private Brisbane hospital between 01/01/2011 and 28/03/2012 with an admission diagnosis of CAP were included. Data were collected on administration time and choice of antibiotic therapy in the ED. This was compared with local and national CAP guidelines. Concordance with antibiotic guidelines was low (6.9%). Antibiotics with broader spectrum of action than that recommended in guidelines were frequently prescribed. Eighty-one percent of patients received their first antibiotic within 4 hours of arriving in the ED. Mortality was low at 0.9% in a cohort where 31% of patients were aged under 65. We found low rates of concordance with CAP antibiotic guidelines and high use of broad-spectrum antibiotics. This has the potential to lead to increased rates of antibiotic resistance. A subtle alteration to the restrictions within the pharmaceutical benefit scheme formulary could potentially decrease the high usage of broad-spectrum antibiotics. However, the low mortality rate, nontoxic nature of these antibiotics, and the ease of their administration pose a challenge to convincing clinicians to alter their practice.

P84 Is The Curb-65 Score A Reliable Tool For Guiding Initial Antibiotic Therapy In Acutely Unwell Patients With Community Acquired Pneumonia?

Introduction Prompt appropriate antibiotics for community acquired pneumonia (CAP) reduces mortality, length of stay and adverse events. Antibiotic choice is directed by the CURB-65 score and clinical judgement.1 Admission is recommended for most CURB-65 ≥2.1 Recent national data showed an unexplained non-compliance of 40% (>2000 patients) with CAP antibiotic guidelines using CURB-65 scores alone. Antimicrobial misuse and resistance are a global concern. We investigated compliance with our Trust CAP guidelines and used an early warning score (EWS)2 to quantify clinical judgement. Methods Data were collected retrospectively for adults attending the emergency department with CAP4 over 4 months. The CURB-65 and the Trust’s EWS (Physiological Observations Track and Trigger system – POTTS)2 were calculated at presentation. A POTTS score of 2 triggers escalation of care. Prescriptions were compliant when the initial antibiotic concurred with the Trust guideline. Patients receiving broader spectrum agents than recommended were ‘over-treated’. Admission was noted. Results (Table 1) Of 77 patients with CAP, 11 (14%) received ‘compliant’ antibiotics (Table 1). 38 (49%) patients were over-treated, 25 (66%) of whom had POTTS ≥2, though 15 (60%) of these patients had low severity CURB-65 of 0–1. Of 49 patients with POTTS ≥2, 27 (55%) had a CURB-65 of 0–1, 26% a CURB-65 of 2. 44% and 68% of those with a CURB-65 of 0 or 1 were admitted, with higher average POTTS than those discharged. Conclusion The majority of patients incorrectly prescribed broad spectrum antibiotics had a CURB-65 score that failed to categorise them as sick enough to warrant them despite an EWS≥2. Hospital admission demonstrated similar findings. Over half of those with an elevated EWS had a low severity CURB-65. We did not collect outcome data but the ‘over-treatment’ and admission appear appropriate. Prompt, effective and empiric antimicrobials for septic patients give better clinical outcomes. Seemingly non-compliant antimicrobial prescriptions may have punitive implications for Trusts. We suggest that CURB-65 under-recognises sepsis syndrome and thus the EWS should be included and further validated in CAP guidelines and audits. Reference BTS CAP guidelines RJ Oakey, V Slade. Physiological observation track and trigger system. Nursing Standard. 2006;20:48–54

Antibiotics for community-acquired pneumonia in adult outpatients.

Lower respiratory tract infection (LRTI) is the third leading cause of death worldwide and the first leading cause of death in low-income countries. Community-acquired pneumonia (CAP) is a common condition that causes a significant disease burden for the community, particularly in children younger than five years, the elderly and immunocompromised people. Antibiotics are the standard treatment for CAP. However, increasing antibiotic use is associated with the development of bacterial resistance and side effects for the patient. Several studies have been published regarding optimal antibiotic treatment for CAP but many of these data address treatments in hospitalised patients. This is an update of our 2009 Cochrane Review and addresses antibiotic therapies for CAP in outpatient settings. To compare the efficacy and safety of different antibiotic treatments for CAP in participants older than 12 years treated in outpatient settings with respect to clinical, radiological and bacteriological outcomes. We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3, 2014), EMBASE (January 1974 to March 2014), CINAHL (2009 to March 2014), Web of Science (2009 to March 2014) and LILACS (2009 to March 2014). We looked for randomised controlled trials (RCTs), fully published in peer-reviewed journals, of antibiotics versus placebo as well as antibiotics versus another antibiotic for the treatment of CAP in outpatient settings in participants older than 12 years of age. However, we did not find any studies of antibiotics versus placebo. Therefore, this review includes RCTs of one or more antibiotics, which report the diagnostic criteria and describe the clinical outcomes considered for inclusion in this review. Two review authors (LMB, TJMV) independently assessed study reports in the first publication. In the 2009 update, LMB performed study selection, which was checked by TJMV and MMK. In this 2014 update, two review authors (SP, SM) independently performed and checked study selection. We contacted trial authors to resolve any ambiguities in the study reports. We compiled and analysed the data. We resolved differences between review authors by discussion and consensus. We included 11 RCTs in this review update (3352 participants older than 12 years with a diagnosis of CAP); 10 RCTs assessed nine antibiotic pairs (3321 participants) and one RCT assessed four antibiotics (31 participants) in people with CAP. The study quality was generally good, with some differences in the extent of the reporting. A variety of clinical, bacteriological and adverse events were reported. Overall, there was no significant difference in the efficacy of the various antibiotics. Studies evaluating clarithromycin and amoxicillin provided only descriptive data regarding the primary outcome. Though the majority of adverse events were similar between all antibiotics, nemonoxacin demonstrated higher gastrointestinal and nervous system adverse events when compared to levofloxacin, while cethromycin demonstrated significantly more nervous system side effects, especially dysgeusia, when compared to clarithromycin. Similarly, high-dose amoxicillin (1 g three times a day) was associated with higher incidence of gastritis and diarrhoea compared to clarithromycin, azithromycin and levofloxacin. Available evidence from recent RCTs is insufficient to make new evidence-based recommendations for the choice of antibiotic to be used for the treatment of CAP in outpatient settings. Pooling of study data was limited by the very low number of studies assessing the same antibiotic pairs. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. However, two studies did find significantly more adverse events with use of cethromycin as compared to clarithromycin and nemonoxacin when compared to levofloxacin. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations. Further studies focusing on diagnosis, management, cost-effectiveness and misuse of antibiotics in CAP and LRTI are warranted in high-, middle- and low-income countries.

Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia.

There are limited U.S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). However, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. A retrospective study of all adults hospitalized with community-onset pneumonia (CAP and HCAP) at a large U.S. medical center from January 2010 to December 2011 was conducted. The objective was to ascertain the rate of pneumonia caused by MDROs and to evaluate whether HCAP is a risk factor for MDRO pneumonia. Univariate and propensity score-adjusted multivariate analyses were performed. A total of 521 patients (50.5% CAP and 49.5% HCAP) were included. The most common etiologies of pneumonia were primary viral and Streptococcus pneumoniae. MDROs were isolated in 20 (3.8%) patients overall, and MDROs occurred in 5.9% and 1.9% of HCAP and CAP patients, respectively. The presence of an MDRO was not associated with HCAP classification (odds ratio [OR]=1.95; 95% confidence interval [95% CI], 0.66 to 5.80; P=0.23) or with most of its individual components (hemodialysis, home infusion, home wound care, and ≥48-h hospitalization in the last 90 days). Independent predictors of MDRO included the following: Pseudomonas aeruginosa colonization/infection in the previous year (OR=7.43; 95% CI, 2.24 to 24.61; P<0.001), antimicrobial use in the previous 90 days (OR=2.90; 95% CI, 1.13 to 7.45; P=0.027), admission from a nursing home (OR=4.19; 95% CI, 1.55 to 11.31; P=0.005), and duration of hospitalization in the previous 90 or 180 days (P=0.013 and P=0.002, respectively). MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empirical overprescribing of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa.

Comparative Effectiveness of Empiric Antibiotics for Community-Acquired Pneumonia

Comparative Effectiveness of Empiric Antibiotics for Community-Acquired Pneumonia

Antibiotics for community-acquired pneumonia in children.

Pneumonia caused by bacterial pathogens is the leading cause of mortality in children in low-income countries. Early administration of antibiotics improves outcomes. To identify effective antibiotic drug therapies for community-acquired pneumonia (CAP) of varying severity in children by comparing various antibiotics. We searched CENTRAL 2012, Issue 10; MEDLINE (1966 to October week 4, 2012); EMBASE (1990 to November 2012); CINAHL (2009 to November 2012); Web of Science (2009 to November 2012) and LILACS (2009 to November 2012). Randomised controlled trials (RCTs) in children of either sex, comparing at least two antibiotics for CAP within hospital or ambulatory (outpatient) settings. Two review authors independently extracted data from the full articles of selected studies. We included 29 trials, which enrolled 14,188 children, comparing multiple antibiotics. None compared antibiotics with placebo.Assessment of quality of study revealed that 5 out of 29 studies were double-blind and allocation concealment was adequate. Another 12 studies were unblinded but had adequate allocation concealment, classifying them as good quality studies. There was more than one study comparing co-trimoxazole with amoxycillin, oral amoxycillin with injectable penicillin/ampicillin and chloramphenicol with ampicillin/penicillin and studies were of good quality, suggesting the evidence for these comparisons was of high quality compared to other comparisons.In ambulatory settings, for treatment of World Health Organization (WHO) defined non-severe CAP, amoxycillin compared with co-trimoxazole had similar failure rates (odds ratio (OR) 1.18, 95% confidence interval (CI) 0.91 to 1.51) and cure rates (OR 1.03, 95% CI 0.56 to 1.89). Three studies involved 3952 children.In children with severe pneumonia without hypoxaemia, oral antibiotics (amoxycillin/co-trimoxazole) compared with injectable penicillin had similar failure rates (OR 0.84, 95% CI 0.56 to 1.24), hospitalisation rates (OR 1.13, 95% CI 0.38 to 3.34) and relapse rates (OR 1.28, 95% CI 0.34 to 4.82). Six studies involved 4331 children below 18 years of age.In very severe CAP, death rates were higher in children receiving chloramphenicol compared to those receiving penicillin/ampicillin plus gentamicin (OR 1.25, 95% CI 0.76 to 2.07). One study involved 1116 children. For treatment of patients with CAP in ambulatory settings, amoxycillin is an alternative to co-trimoxazole. With limited data on other antibiotics, co-amoxyclavulanic acid and cefpodoxime may be alternative second-line drugs. Children with severe pneumonia without hypoxaemia can be treated with oral amoxycillin in an ambulatory setting. For children hospitalised with severe and very severe CAP, penicillin/ampicillin plus gentamycin is superior to chloramphenicol. The other alternative drugs for such patients are co-amoxyclavulanic acid and cefuroxime. Until more studies are available, these can be used as second-line therapies.There is a need for more studies with radiographically confirmed pneumonia in larger patient populations and similar methodologies to compare newer antibiotics. Recommendations in this review are applicable to countries with high case fatalities due to pneumonia in children without underlying morbidities and where point of care tests for identification of aetiological agents for pneumonia are not available.

Biomarkers and Community-Acquired Pneumonia: Tailoring Management with Biological Data

Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases worldwide, with an incidence of 0.3 to 0.5% in the adult population. A new diagnostic and prognostic approach relies on evaluation of biomarkers as an expression of the host's inflammatory response against the microorganism. C-reactive protein (CRP), procalcitonin (PCT), and cytokines are the most frequently studied, whereas pro-adrenomedullin (pro-ADM), pro-vasopressin (pro-VNP), and others are currently obtaining promising results. Their usefulness for diagnosis is limited, although PCT has been successfully used to guide prescription of antibiotics in patients with suspected CAP. Nevertheless, the accuracy of PCT in distinguishing between bacterial or viral infection and safely withholding antibiotics in CAP is the subject of debate. Analysis of systemic biomarkers in addition to clinical scores [Pneumonia Severity Index (PSI) or CURB-65 (confusion, urea, respiratory, blood pressure, >65 years)/CRB-65 (confusion, respiratory, blood pressure)] has been shown to improve 30 day mortality prediction and absence of severe complications. Pro-ADM is probably the biomarker that correlates most strongly with mortality prediction. During treatment, ~15% of hospitalized CAP patients develop treatment failure, and almost 6% may manifest rapidly progressive pneumonia. Initially increased and persistent raised levels of biomarkers and cytokines have been shown to identify patients at risk of treatment failure, thereby aiding clinical management. Data from the literature appear to support the use of biomarkers in routine clinical practice to improve the decision making in CAP.