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Concerns about inadequate performance and complexity limit routine use of clinical risk scores in lower respiratory tract infections. Our aim was to study feasibility and effects of adding the biomarker proadrenomedullin (proADM) to the confusion, urea >7 mmol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure, Proof-of-concept trial: how to shorten LOS in patients with LRTIs by reducing medically unnecessary days in the hospital http://ow.ly/nI7z4

Background: Despiteits recommendation in management guide lines for community acquired pneumonia (CAP), the CURB65 score is frequently not followed for disposition decisions in clinical routine. We therefore proposed an improved CURB65 A score, supplemented by proadre nome dull in (ProADM) levels for patients with CAP and other lower respiratory tract infections (LRTIs). In this study, we vali dated this risk based biomarker enhanced disposition in patients with LRTIs presenting to the emergency department of the University Hospital of Basel. Methods: In this prospective observational cohort study of 85 patients presenting with LRTIs, site of care was decided by the physicians in charge according to their judgement. Retro spectively the CURB65 A score was calculated and a virtual disposition assigned. This was compared with the existing disposition in order to identify efficacy of the novel risk based biomarker enhanced disposition. Results: The novel disposition criteria considered 14 patients suitable for outpatient treatment compared to 11 in the current disposition (p = 0.5). It detected 7 patients to be best treated outside the hospital for nursing reasons, while the current disposition detected only 1 patient requiring geriatric care (p = 0.09). Further, it decreased regular hospitalizations considerably (32 vs. 64, p 0.001). Conclusions: The novel risk based biomarker enhanced disposition is an objective, safe and probably more efficient disposition system to identify outpatient treatment options than the current practice at the University Hospital of Basel.

Background The aim of this study was to determine the prognostic utility of serial measurement of the cardiovascular biomarker midregion proadrenomedullin (MR-proADM) in patients admitted with lower respiratory tract infection. In a previous trial in dyspneic patients (BACH trial) we could show that serial measurement of MR-proADM proves useful for risk assessment and patient monitoring. Models designed to evaluate serial biomarker measurements usually fail to answer two fundamental questions necessary to judge their clinical relevance: whether serial measurements provide additional information on top of the first measurement, and, if yes, at which time point a re-evaluation may be clinically useful. Method We apply an adapted time-dependent Cox model to data from the ProHosp trial, a prospective trial, which was observational in regards to application of prognostic biomarkers, where blood draws for biomarker evaluation were collected at day of patient inclusion, days 3, 5 and 7. In this trial, the cardiovascular biomarker MR-proADM was evaluated for its ability to predict survival in comparison to clinical risk scores. Results With the adapted time-dependent Cox model, we could demonstrate a significant added value of the follow up measurements on top of that obtained on admission. Despite a high correlation between serial measurements, the gain can be observed as early as 3days after inclusion. We illustrate the added prognostic value and clinical relevance of re-evaluation via Kaplan–Meier plots. Conclusion We could demonstrate that the prognostic biomarker MR-proADM can potentially serve as a outcome monitoring marker in patients admitted with lower respiratory tract infections.

Introduction: OPTIMA is a multi-professional quality management and research project, conducted at the Cantonal Hospital of Aarau (KSA), Switzerland in cooperation with post-acute care institutions from November 2009 until December 2012. Objective: The goal of this study was to optimize patient care pathways and to provide patient-centered, costeffective care that is conform with the introduction of the Diagnosis Related Groups (DRG) in 2012. Methods: The “Post-Acute Care Discharge Scores” (PACD) was applied to assess the risk for transfer to postacute care facilities in 240 patients suffering from lower respiratory tract infections during the first phase of the study (OPTIMA I) from October 2009 until April 2010. In order to assess the patients’ self-care ability, the “Self-Care Index” (SPI) tool was applied on admission and during the course of inpatient treatment. Results: The PACD predicted that 55% of patients (N=202) were at medium to high risk of requiring post-acute care. According to the SPI, 38% of patients (N=217) showed reduced ability to care for themselves. The discharge of 69% of medically stable patients (N=43) was postponed due to shortage of beds in post-acute care facilities. Correspondingly, 62% of the medically stable patients (N=141) could imagine receiving post-acute care in a “Nurseled Unit” (NLU). Despite being medically stable, one third of the patients (N=124) was not ready to return to their homes because they felt too weak or insecure to cope with everyday life. Conclusion: Using standardized tools to predict patients at risk for transfer to post-acute care facilities and reduced self-care abilities and the continuous evaluation of medical stability are all methods that could be applied to enhance interdisciplinary care and optimize discharge management. Furthermore, setting up NLU is expected to unburden the occupancy of acute care beds by a considerable amount of patients who are in need of post-acute care.

International audience; For epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other serotypes carried. Here, we describe a novel, rapid multiplex real-time PCR assay for identification and quantification of the 40 most prevalent pneumococcal serotypes and the assay impacts in pneumonia specimens from emerging and developing countries. Eleven multiplex PCR to detect 40 serotypes or serogroups were optimized. Quantification was enabled by reference to standard dilutions of known bacterial load. Performance of the assay was evaluated to specifically type and quantify S. pneumoniae in nasopharyngeal and blood samples from adult and pediatric patients hospitalized with pneumonia (n = 664) from five different countries. Serogroup 6 was widely represented in nasopharyngeal specimens from all five cohorts. The most frequent serotypes in the French, South African, and Brazilian cohorts were 1 and 7A/F, 3 and 19F, and 14, respectively. When both samples were available, the serotype in blood was always present as carriage with other serotypes in the nasopharynx. Moreover, the ability of a serotype to invade the bloodstream may be linked to its nasopharyngeal load. The mean nasopharyngeal concentration of the serotypes that moved to the blood was 3 log-fold higher than the ones only found in the nasopharynx. This novel, rapid, quantitative assay may potentially predict some of the S. pneumoniae serotypes invasiveness and assessment of pneumococcal serotype distribution.

OBJECTIVES: The Risk of Early Admission to the Intensive Care Unit (REA-ICU) index is a clinical prediction model that was derived based on 4,593 patients with community-acquired pneumonia (CAP) for predicting early admission to the intensive care unit (ICU; i.e., within 3 days following emergency department [ED] presentation). This study aimed to validate the REA-ICU index in an independent sample. METHODS: The authors retrospectively stratified 850 CAP patients enrolled in a multicenter prospective randomized trial conducted in Switzerland, using the REA-ICU index, alternate clinical prediction models of severe pneumonia (SMART-COP, CURXO-80, and the 2007 IDSA/ATS minor severity criteria), and pneumonia severity assessment tools (the Pneumonia Severity Index [PSI] and CURB-65). Results: The rate of early ICU admission did not differ between the validation and derivation samples within each risk class of the REA-ICU index, ranging from 1.1% to 1.8% in risk class I to 27.1% to 27.6% in risk class IV. The areas under the receiver operating characteristic (ROC) curve were 0.76 (95% confidence interval [CI] = 0.70 to 0.83) and 0.80 (95% CI = 0.77 to 0.83) in the validation and derivation samples, respectively. In the validation sample, the REA-ICU index performed better than the pneumonia severity assessment tools, but failed to demonstrate an accuracy advantage over alternate prediction models in predicting ICU admission. CONCLUSIONS: The REA-ICU index reliably stratifies CAP patients into four categories of increased risk for early ICU admission within 3 days following ED presentation. Further research is warranted to determine whether inflammatory biomarkers may improve the performance of this clinical prediction model.

Study objective: Syncope is one of the most common presentation of patients seen in emergency departments (ED). Risk assessment of syncope is challenging. The San Francisco Syncope Rule is the most widely used risk assessment, but has moderate accuracy. The aim of our study was to investigate blood biomarkers as prognostic factors for adverse outcome. Methods: In this observational study we included consecutive adults presenting with syncope to our ED. Management decisions were left to the discretion of the treating physicians. Patients were monitored for adverse events until discharge and underwent a phone interview 30 days after enrolment. Adverse outcome was defined as recurrent syncope, rehospitalization and death within 30 days. Results: We included 132 adult patients of whom 19 (14%) had an adverse event (recurrent syncope = 3, rehospitalisation = 12, death = 4). No difference in the San Francisco Syncope Rule was found in patients with and without adverse events (SFSR ≥ 1: 37% vs. 39%, p = 0.877). Median levels of ProADM (1.23 vs. 0.81 nmol/l; p = 0.006) and NT-proBNP (454 vs 134ng/l; p = 0.035) were higher and median levels for cholesterol (3.68 vs 4.57 mmol/l; p = 0.008) and prealbumin (0.19 vs0.26 g/l; p = 0.005) were lower in patients with adverse events. Prealbumin (AUC 0.72) and ProADM (AUC 0.70) had the highest prognostic accuracy. Conclusion: Biomarkers predicted poor outcome and might be helpful in the context of a clinical algorithm for an improved triage of syncope patients in the ED.

Background. There is major need for a more sensitive assay for the diagnosis of pneumococcal community-acquired pneumonia (CAP). We hypothesized that pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration followed by pneumonia. We therefore tested a quantitative lytA real-time polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia and controls. Methods. In the absence of a sensitive reference standard, a composite diagnostic standard for pneumococcal pneumonia was considered positive in South African human immunodeficiency virus (HIV)–infected adults hospitalized with radiographically confirmed CAP, if blood culture, induced good-quality sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of quantitative lytA rtPCR in NP swab samples were compared with quantitative colony counts in patients with CAP and 300 HIV-infected asymptomatic controls. Results. Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP (27.1%) using the composite diagnostic standard. NP colonization density measured by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0 log10 copies/mL, compared with patients with CAP outside the composite standard (2.7 log10 copies/mL; P < .001) and asymptomatic controls (0.8 log10 copies/mL; P < .001). A lytA rtPCR density ≥8000 copies/mL had a sensitivity of 82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from asymptomatic colonization. The proportion of CAP cases attributable to pneumococcus increased from 27.1% to 52.5% using that cutoff. Conclusions. A rapid molecular assay of NP pneumococcal density performed on an easily available specimen may significantly increase pneumococcal pneumonia diagnoses in adults.

All published evidence on procalcitonin (PCT)-guided antibiotic therapy was obtained in trials where physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study investigates the effectiveness of PCT guidance in an observational quality control survey. We monitored antibiotic therapy and algorithm adherence in consecutive patients with respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland, between May 2008 and February 2009. The results were compared to the site-specific results of the former ProHOSP study. Overall and more pronounced for patients with community-acquired pneumonia, the median duration of antibiotic treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7 days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics were administered according to the prespecified PCT algorithm. No significant differences concerning adverse medical outcome could be detected. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process of the prescribing physicians.

After a primary series of 3 doses, it was found that a 9-valent pneumococcal conjugate vaccine no longer reduces nasopharyngeal colonization by vaccine serotypes in children 5.3 years of age. In addition, human immunodeficiency virus (HIV)-infected children (n=81) had a higher prevalence of colonization by Streptococcus pneumoniae and Haemophilus influenzae (71.6% and 74.1%, respectively) than did HIV-uninfected children (n=271; 50.9% and 52.0%, respectively), suggesting that increased colonization may contribute to the greater burden of pneumococcal disease in HIV-infected children. Inverse associations between colonization by S. pneumoniae and colonization by Staphylococcus aureus and between colonization by S. aureus and colonization by H. influenzae were observed only in HIV-uninfected children, possibly as a result of suboptimal adaptive immunity after previous colonization in HIV-infected children.

Background Urinary tract infections (UTIs) are common drivers of antibiotic use. The minimal effective duration of antibiotic therapy for UTIs is unknown, but any reduction is important to diminish selection pressure for antibiotic resistance, costs, and drug-related side-effects. The aim of this study was to investigate whether an algorithm based on procalcitonin (PCT) and quantitative pyuria reduces antibiotic exposure. Methods From April 2012 to March 2014, we conducted a factorial design randomized controlled open-label trial. Immunocompetent adults with community-acquired non-catheter-related UTI were enrolled in the emergency department of a tertiary-care 600-bed hospital in northwestern Switzerland. Clinical presentation was used to guide initiation and duration of antibiotic therapy according to current guidelines (control group) or with a PCT-pyuria-based algorithm (PCT-pyuria group). The primary endpoint was overall antibiotic exposure within 90 days. Secondary endpoints included duration of the initial antibiotic therapy, persistent infection 7 days after end of therapy and 30 days after enrollment, recurrence and rehospitalizations within 90 days. Results Overall, 394 patients were screened, 228 met predefined exclusion criteria, 30 declined to participate, and 11 were not eligible. Of these, 125 (76% women) were enrolled in the intention-to-treat (ITT) analysis and 96 patients with microbiologically confirmed UTI constituted the per protocol group; 84 of 125 (67%) patients had a febrile UTI, 28 (22%) had bacteremia, 5 (4%) died, and 3 (2%) were lost to follow-up. Overall antibiotic exposure within 90 days was shorter in the PCT-pyuria group than in the control group (median 7.0 [IQR, 5.0–14.0] vs. 10.0 [IQR, 7.0–16.0] days, P = 0.011) in the ITT analysis. Mortality, rates of persistent infections, recurrences, and rehospitalizations were not different. Conclusions A PCT-pyuria-based algorithm reduced antibiotic exposure by 30% when compared to current guidelines without apparent negative effects on clinical outcomes. Trial registration Current controlled trials ISRCTN13663741, date applied: 22/05/2012, date assigned: 03/07/2012, last edited: 28/01/2014. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0347-y) contains supplementary material, which is available to authorized users.

A 33-year-old man with a known bicuspid aortic valve presented with fever, chills, progressive fatigue, anorexia, and night sweats. Echocardiography confirmed aortic-valve endocarditis, but blood cultures remained negative. Bartonella henselae endocarditis was ultimately confirmed by serology as well as by immunohistochemistry and PCR testing of the excised valve. The patient recovered with appropriate antibiotic therapy. B henselae is a common cause of culture-negative endocarditis. It predominantly affects men with underlying valvular disease, and has a predilection for aortic valves. Diagnosis is usually made serologically and with either tissue culture, immunohistochemistry, or PCR. Treatment of this destructive endocarditis consists of a combination of long-term antibiotic therapy and surgical valve repair. This case is used to discuss the approach towards the treatment of patients with endocarditis that is blood-culture negative.

We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S. pneumoniae (MRSP), and macrolide-resistant S. pyogenes (MRGAS) in 20 countries. Total antibiotic use was correlated with PNSP (r = 0.75; p < 0.001), as was macrolide use with MRSP (r = 0.88; p < 0.001) and MRGAS (r = 0.71; p = 0.004). Streptococcal resistance is directly associated with antibiotic selection pressure on a national level.

The Programme for International Student Assessment (PISA) 2000 study assessed a wide range of knowledge and skills attained by 265,000 15-year-olds in 32 industrialized countries. One survey unit of the scientific literacy section addressed infection control issues, based on Semmelweis' landmark research on the causes and prevention of puerperal fever. The present report describes the questions and student performance for this infection control exercise set and evaluates performance variability between countries.

Quantitative lytA real-time PCR (rtPCR) results from nasopharyngeal (NP) swabs distinguish community-acquired pneumococcal pneumonia (CAP) from asymptomatic colonization. The use of an optimized cutoff value improved pneumococcal etiology determination compared to that of traditional diagnostic methods. Here, we compare the utility of lytA rtPCR from induced sputum and from NP swabs. Pneumococcus was considered the cause of CAP in HIV-infected South African adults if blood culture, induced-sputum culture or Gram stain, urine antigen test, or whole-blood lytA rtPCR revealed pneumococcus or if lytA rtPCR from NP swabs gave a result of >8,000 copies/ml. lytA rtPCR was also performed on induced sputum. Pneumococcus was detected by lytA rtPCR from sputum in 149 (67.1%) of 222 patients with available induced sputum, whereas the results of either Gram stain or culture of sputum were positive in 105 of 229 patients (45.9%; P < 0.001). The mean copy numbers from sputum were higher when the sputum cultures were positive than when the sputum cultures were negative (7.9 versus 5.6 log 10 copies/ml; P < 0.001). Against the composite diagnostic standard, a cutoff value of 10,000 copies/ml for good-quality sputum lytA rtPCR had a sensitivity of 78.1% and a specificity of 80.0%. This cutoff value performed similarly to the previously identified cutoff value of 8,000 copies/ml for NP swab lytA rtPCR (area under the curve receiver operating characteristic [AUC-ROC], 80.4% for sputum of any quality versus 79.6% for NP swabs). The AUC-ROC for good-quality sputum was 83.2%. Overall, lytA rtPCR performs similarly well on induced sputum as on NP swabs for most patients but performs slightly better if good-quality sputum can be obtained. Due to the ease of specimen collection, NP swabs may be preferable for the diagnosis of pneumococcal pneumonia.

The impact of chronic lung diseases on outcome in community-acquired pneumonia (CAP) is not well established. We aimed to investigate the outcome of adult CAP-patients with underlying chronic obstructive pulmonary disease (COPD), asthma or interstitial lung disease (ILD) in a case-control study.We used a nationwide database including all hospitalisations in Switzerland from 2002 to 2010. Endpoints were the incidence of lung abscess, parapneumonic pleural effusion, empyema, acute respiratory distress syndrome, in-hospital mortality and length of stay.We found less disease-related complications of CAP in COPD (n = 17,075) and asthma (n = 2700) patients compared with their controls. This difference was mainly related to a lower incidence of pleural effusion (COPD: 4.3% vs 4.9%, p = 0.011; asthma: 3.4% vs 5.2%, p0.001). In-hospital mortality was lower in the COPD and - much more pronounced - asthma cohorts (COPD: 5.8% vs 6.7%, p0.001; asthma: 1.4% vs 4.8%, p0.001). For ILD (n = 916), the complication rate was similar as compared to the control group, whereas in-hospital mortality was markedly higher (16.3% vs 6.8%, p0.001).These rather unexpected results should be viewed as hypothesis generating, with various possible explanations for our findings. These include the possible influence of inhaled corticosteroid therapy, a possibly higher awareness of general practitioners and hospital physicians while treating patients with chronic lung diseases, a different infective agent spectrum or a different immune response.

Background Medical textbooks often list Legionnaires’ disease as a differential diagnosis of the syndrome of inappropriate secretion of anti-diuretic hormone (ADH) (SIADH), but evidence supporting this association is largely lacking. We tested the hypothesis whether hyponatremia in patients with Legionnaires’ disease would be caused by increased CT-ProVasopressin. Methods We measured CT-ProVasopressin and sodium levels in a prospective cohort of 873 pneumonia patients from a previous multicentre study with 27 patients having positive antigen tests for Legionella pneumophila. Results Patients with Legionnaires’ disease more frequently had low sodium levels (Na Conclusion While Legionnaires’ disease was associated with hyponatremia, no concurrent increase in CT-ProVasopressin levels was found, which argues against elevated ADH levels as the causal pathway to hyponatremia. Rather, Vasopressin precursors were upregulated as response to stress in severe disease, which seems to overrule the osmoregulatory regulation of ADH.

International audience; BACKGROUND: Whether proadrenomedullin (ProADM) improves the performance of the Risk of Early Admission to ICU (REA-ICU) score in predicting early, severe community-acquired pneumonia (ESCAP) has not been demonstrated. METHODS: Secondary analysis was completed of the original data from 877 consecutive patients with community-acquired pneumonia (CAP) enrolled in the Procalcitonin-Guided Antibiotic Therapy and Hospitalization in Patients With Lower Respiratory Tract Infections (ProHOSP) study, a multicenter trial in EDs of six tertiary-care hospitals in Switzerland. ESCAP was defined by either the requirement for mechanical ventilation or vasopressive drugs or occurrence of death within 3 days of ED presentation. RESULTS: Eighty patients (9.1%) developed ESCAP (47 required mechanical ventilation, 19 vasopressive drugs, and 16 died) within 3 days of ED presentation. They had a higher median ProADM value (2.18 nmol/L vs 1.15 nmol/L, P < .001). Combining ProADM testing with the REA-ICU score improved the area under the curve (0.81) compared with either parameter (ProADM [0.73] or REA-ICU score [0.76], P < .001) and resulted in a net reclassification improvement of 0.20 (P < .001). A ProADM value ≥ 1.8 nmol/L or assignment to REA-ICU risk classes III-IV predicted ESCAP with a sensitivity of 76.3% and a negative predictive value of 96.7%. Excluding 21 patients with major criteria of severe CAP on presentation showed similar results. CONCLUSION: These study findings demonstrate that the addition of ProADM to the REA-ICU score improves the classification of a substantial proportion of patients in the ED at intermediate or high risk for ESCAP, which may translate into better triage decisions.

Certaines etudes cliniques ont montre que la determination du marqueur sanguin procalcitonine pourrait permettra une meilleure personnalisation des antibiotherapies. L’interet de cette approche a notamment ete demontre chez les patients avec infections des voies respiratoires et hospitalises en unites de soins intensifs.

Klinische Studien haben ergeben, dass der Blutmarker Procalcitonin eine auf den Patienten abgestimmte personalisierte Antibiotikatherapie erlaubt. Dies wurde insbesondere bei Patienten mit Atemwegsinfektionen und auf Intensivstation gezeigt.

Background: Acute decompensated heart failure (ADHF) causes a substantial burden for health care systems. Data to rationally define the need for hospitalization or the appropriate length of stay (LOS) is limited. Our aim was to personalize length of stay in patients admitted to hospital for acute decompensated heart failure. Methods: Consecutive patients with ADHF presenting to our emergency department were prospectively followed. We daily conducted a multidisciplinary risk assessment and compared proposed with actually observed triage decisions. Results: At presentation, all patients required hospitalization. Median LOS was 11 days including 1 day after reaching medical stability. In 42.7% of patients, hospitalization was prolonged after medical stability mainly for nursing and organizational reasons. Within 30 days of enrollment, 7 (9.3%) patients were rehospitalized, 3 of them for persisting or relapsing heart failure. Conclusions: There appears to be potential to shorten inhospital stay in patients with ADHF mainly by providing post discharge ambulatory nursing care in order to improve resource utilization and to diminish “hospitalization-associated disability”. doi: http://dx.doi.org/10.4021/jocmr1154w

In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life.We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days.Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P.001), outpatients (86.1%) and inpatients (65.9%) (P.001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P.001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P.001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P.001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07).This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts.isrctn.org Identifier: ISRCTN40854211.

There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms.

Summary PRINCIPLES: Reimbursement for inpatient treatment in Switzerland is in transition. While hospitals in some cantons already use Diagnosis Related Groups (DRG) based systems for hospital financing, others use fee-for-service (FFS) based systems, a situation that provides the opportunity to perform a head-to-head comparison between the two reimbursement systems. The aim of this analysis was to compare reimbursement systems with regard to length of hospital stay (LOS) and patient outcomes in a cohort of community-acquired pneumonia patients from a previous prospective multicentre study in Switzerland. METHODS: This is a post-hoc analysis of 925 patients with community-acquired pneumonia from a previous randomised-controlled trial. We calculated multivariate regression models adjusted for age, gender, comorbidities and severity of illness (using the Pneumonia Severity Index) and accounting for clustering within hospitals to compare LOS and outcomes between FFS (n = 4) or DRG hospitals (n = 2). RESULTS: LOS in DRG hospitals was significantly shorter compared to FFS hospitals (8.4 vs 10.3 days, absolute difference 1.9 days [95%CI 0.8–3.1]). This was confirmed in multivariate adjusted Cox models (hazard ratio 1.2 [95% 1.1–1.3]). There were no differences in 30-day and 18-month mortality rates (adjusted odds ratio 1.7 [95% 0.9–3.2] and 1.3 [95% 0.9–1.9]) or recurrence rates within 30 days (adjusted odds ratio 0.8 [95% 0.4–1.7]). Also, no differences were found in the rate of still ongoing clinical symptoms at 30 days, satisfaction with the discharge process and quality of life measures at 30 days of follow-up. CONCLUSIONS: This study focusing on community-acquired pneumonia patients with different severities found a 20% shorter LOS in hospitals with DRG financing compared to FFS hospitals without apparent harmful effects on patient outcomes, satisfaction with care and different quality of life measures. Further studies are required to validate these findings for other medical and surgical patient populations.

Evaluation of: Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM. Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am. J. Clin. Pathol. 135(2), 182-189 (2011). In a recent report, Riedel et al. proposed a procalcitonin cutoff of 0.1 ng/ml to rule out bacteremia in adult patients presenting to the emergency department with systemic infections. Procalcitonin levels were higher in patients with true bacteremia than in patients with negative blood cultures or bacteremia due to possible contaminants. For prediction of bacteremia, a procalcitonin level of 0.1 ng/ml had an excellent negative predictive value of 96.3%, and a good sensitivity of 75%, specificity of 70.6% and area under the curve of 0.73, but poor positive predictive value of 12.8%. Based on the results in this study, we propose that a procalcitonin value of 0.1 ng/ml or less could be used to rule out bacteremia (NPV: 96.3%).

Background Proadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI. Methods We used data of 1359 patients with LRTI enrolled in a multicenter study. We chose two ProADM cut-off values by assessing the association between ProADM levels and the risk of adverse events and mortality. A composite score (CURB65-A) was created combining CURB65 classes with ProADM cut-offs to further risk-stratify patients. Results CURB65 and ProADM predicted both adverse events and mortality similarly well in CAP and non-CAP-LRTI. The combined CURB65-A risk score provided better prediction of death and adverse events than the CURB65 score in the entire cohort and in CAP and non-CAP-LRTI patients. Within each CURB65 class, higher ProADM-levels were associated with an increased risk of adverse events and mortality. Overall, risk of adverse events (3.9%) and mortality (0.65%) was low for patients with CURB65 score 0-1 and ProADM ≤0.75 nmol/l (CURB65-A risk class I); intermediate (8.6% and 2.6%, respectively) for patients with CURB65 score of 2 and ProADM ≤1.5 nmol/l or CURB classes 0-1 and ProADM levels between 0.75-1.5 nmol/L (CURB65-A risk class II), and high (21.6% and 9.8%, respectively) for all other patients (CURB65-A risk class III). If outpatient treatment was recommended for CURB65-A risk class I and short hospitalization for CURB65-A risk class II, 17.9% and 40.8% of 1217 hospitalized patients could have received ambulatory treatment or a short hospitalization, respectively. Conclusions The new CURB65-A risk score combining CURB65 risk classes with ProADM cut-off values accurately predicts adverse events and mortality in patients with CAP and non-CAP-LRTI. Additional prospective cohort or intervention studies need to validate this score and demonstrate its safety and efficacy for the management of patients with LRTI. Trial Registration Procalcitonin-guided antibiotic therapy and hospitalisation in patients with lower respiratory tract infections: the prohosp study; isrctn.org Identifier: ISRCTN: ISRCTN95122877

Procalcitonin is a surrogate biomarker for estimating the likelihood of a bacterial infection. Procalcitonin-guided initiation and termination of antibiotic therapy is a novel approach utilized to reduce antibiotic overuse. This is essential to decrease the risk of side effects and emerging bacterial multiresistance. Interpretation of procalcitonin levels must always comprise the clinical setting and knowledge about assay characteristics. Only highly sensitive procalcitonin assays should be used in clinical practice and cut-off ranges must be adapted to the disease and setting. Highly sensitive procalcitonin measurements, embedded in diagnosis-specific clinical algorithms, have been shown to markedly reduce the overuse of antibiotic therapy without increasing risk to patients in 11 randomized controlled trials including over 3500 patients from different European countries. In primary care and emergency department patients with mild and mostly viral respiratory infections (acute bronchitis), the initial prescription of antibiotics was reduced by 30-80%. In hospitalized and more severely ill patients with community-acquired pneumonia and sepsis, the main effect was a reduction of the duration of antibiotic courses by 25-65%. This review aims to provide physicians with an overview of the strengths and limitations of procalcitonin guidance for antibiotic therapy when used in different clinical settings and in patients with different underlying infections.

There is ongoing controversy about the role of health-care workers in transmission of meticillin-resistant Staphylococcus aureus (MRSA). We did a search of the literature from January, 1980, to March, 2006, to determine the likelihood of MRSA colonisation and infection in health-care workers and to assess their role in MRSA transmission. In 127 investigations, the average MRSA carriage rate among 33 318 screened health-care workers was 4.6%; 5.1% had clinical infections. Risk factors included chronic skin diseases, poor hygiene practices, and having worked in countries with endemic MRSA. Both transiently and persistently colonised health-care workers were responsible for several MRSA clusters. Transmission from personnel to patients was likely in 63 (93%) of 68 studies that undertook genotyping. MRSA eradication was achieved in 449 (88%) of 510 health-care workers. Subclinical infections and colonisation of extranasal sites were associated with persistent carriage. We discuss advantages and disadvantages of screening and eradication policies for MRSA control and give recommendations for the management of colonised health-care workers in different settings.

Current diagnostic tests lack sensitivity for the identification of the bacterial etiology of pneumonia. Attempts during the past 2 decades to improve sensitivity of detection of bacterial constituents in blood by use of antibody-antigen complexes and polymerase chain reaction have been disappointing. Recent data using pneumococcal conjugate vaccines as probes suggest that increased levels of both C-reactive protein and procalcitonin may be useful adjuncts to chest radiographs in the selection of patients with presumed bacterial pneumonia for inclusion in clinical trials. Among pneumococcal diagnostics currently under investigation, quantitative real-time polymerase chain reaction of respiratory secretions, as well as urinary antigen detection and pneumococcal surface adhesin A serological analysis for adults, are candidates for use in future clinical trials of antibiotics.

Background Apart from leukocytosis, few laboratory markers suggestive of Clostridium difficile infections have been described. Methods We retrospectively analyzed the association between thrombocytosis, leukocytosis and C. difficile infections at the Atlanta Veterans Affairs Medical Center. Results Of 162 patients with C. difficile infection, 36 (22%) had thrombocytosis, and 97 (60%) had leukocytosis. C difficile toxin A ELISA was performed in 46/695 (6.6%) patients with thrombocytosis and was positive in 18 (39.1%). Leukocytosis was present in 16/18 (89%) of patients with positive C. difficile toxin A ELISA and thrombocytosis, but also in 21/28 (75%) of patients with negative C. difficile toxin A ELISA and thrombocytosis. Among patients with marked leukocytosis, C. difficile toxin A was more frequently detected in those with concomitant thrombocytosis (P = 0.07). Conclusions The presence of thrombocytosis may be helpful to improve the pretest probability for C difficile infections.

The global epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is heterogeneous.

Summary Antibiotic resistance has become a worldwide problem. However, the reasons for the uneven geographic distribution of antibiotic-resistant microorganisms are not fully understood. For instance, there are striking differences in the epidemiology of multiresistant Gram-positive cocci between the USA and Germany. According to recent reports, the prevalence of high-level penicillinresistant pneumococci (PRP), meticillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in clinically relevant isolates of hospitalised patients in the USA and Germany are: PRP, 14% versus less than 1%; MRSA, 36% versus 15%; and VRE, 15% versus 1%. These disparities may be explained by several determinants: (1) diagnostic practice and laboratory recognition (all three pathogens); (2) clonal differences and pathogen transmissibility (VRE); (3) antibiotic prescribing practices (all three pathogens); (4) population characteristics, including extensive daycare exposure in the USA (PRP); (5) cultural factors (all three pathogens); (6) factors related to the health-care and legal system (all three pathogens); and (7) infectioncontrol practices (MRSA and VRE). Understanding these determinants is important for preventing further spread of multiresistant cocci within the USA. A rational approach to national surveillance is urgently needed in Germany to preserve the favourable situation and decrease MRSA transmission. Finally, we suggest that a macro-level perspective on antibiotic resistance can broaden the understanding of this worldwide calamity, and help prevent further dissemination of multiply resistant microorganisms.

Objective: A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. Methods: Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. Results: There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p

The important study by Lisa McNally and colleagues challenges the validity of the WHO recommendations for empirical antibiotic treatment of HIV-infected children with pneumonia. It is however important to recognise the limited options for improving these recommendations given the complexity of the causes of pneumonia among children for whom treatment fails. In particular changes of antibiotic regimen alone would be unlikely to improve treatment failure in children infected with respiratory viruses (33%). Some of the pneumonias caused by both pneumococci and respiratory viruses might however be preventable by vaccination with pneumococcal conjugate vaccines. Additionally the identification of Pneumocystis jirovecii as the most significant pathogen in infants with treatment failure despite empirical treatment as recommended by WHO confirms the limited success of treating HIV-infected children with severe P jirovecii pneumonia. The higher prevalence (15%) of Mycobacterium tuberculosis in this study than in three other studies (8% each) might be related to a greater sensitivity of methods used for sample collection and an increasing burden of tuberculosis. Nevertheless the observation that M tuberculosis was identified in 21.8% of children with treatment failure perhaps merits most attention. Of particular noteworthiness is that all the studies focused on children with an acute illness challenging the numerous clinical algorithms used for making a clinical diagnosis of pulmonary tuberculosis and the notion that this disorder rarely presents acutely. The management of childhood pulmonary tuberculosis deserves greater priority and is the one issue that can and should be addressed more urgently. We believe tuberculosis should be included in both diagnostic and therapeutic algorithms for acute childhood pneumonia in areas with high HIV and tuberculosis prevalence. (full text)

BACKGROUND: Current medical scores have limited efficiency and safety profiles to enable assignment to the most appropriate treatment site in patients with lower respiratory tract infections (LRTIs). We describe our current triage practice and assess the potential of a combination of CURB65 with proadrenomedullin (ProADM) levels for triage decisions. METHODS: Consecutive patients with LRTIs presenting to our emergency department were prospectively followed and retrospectively classified according to CURB65 and ProADM levels (CURB65-A). Low medical risk patients were further subgrouped according to biopsychosocial and functional risks. We compared the proportion of patients virtually allocated to triage sites with actual triage decisions and assessed the added impact of ProADM in a subgroup. RESULTS: Overall, 93% of 146 patients were hospitalised. Among the 138 patients with available CURB65-A, 17.4% had a low medical risk indicating possible treatment in an outpatient or non-acute medical setting; 34.1% had an intermediate medical risk (short-hospitalisation); and 48.6% had a high medical risk (hospitalisation). Fewer patients were in a low CURB65-A class (I) than a low CURB65 class (0,1) (17.4% vs. 46.3%, p >0.001). Mean length of hospitalisation was 9.8 days including 3.6 days after reaching medical stability. In 60.3% of patients, hospitalisation was prolonged after medical stability mainly for medical reasons. CONCLUSIONS: Current rates of hospitalisation are high in patients with LRTI and length of stay frequently extended beyond time of medical stabilization. The lower proportion of patients reclassified as low risk by adding ProADM to the CURB65 score might improve confidence in the triage algorithm.

Classical biomarkers like C-reactive protein (CRP) or the leucocyte count are only inaccurate tools for predicting the severity of community-acquired pneumonia (CAP). Procalcitonin (PCT) was found to predict 28-day mortality in CAP (area under the curve (AUC) 0.8) similar to the combination of PCT and CRB65 score (AUC 0.83) [1]. Novel prognostic biomarkers, such as Pro-ET1 and MR-ProADM, were shown to correlate with CAP severity [2]. We aimed to compare the diagnostic accuracy to predict mortality and ICU admission of clinical severity scores, biomarkers and their combination.

A procalcitonin (PCT) algorithm was demonstrated to reduce antibiotic exposure in patients with lower respiratory tract infections (LRTI) in several randomised controlled trials. Data on the efficacy of PCT-guided antibiotic stewardship in real life and outside study conditions are lacking.

Introduction The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients. Methods All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to 1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days. Results A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome. Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine. Annotation Results were previously published in German in Anaesthesist 2008; 57: 571–577 (PMID: 18463831). Trial registration ISRCTN10288268

Background Urinary tract infections (UTIs) are among the most common infectious diseases and drivers of antibiotic use and in-hospital days. A reduction of antibiotic use potentially lowers the risk of antibiotic resistance. An early and adequate risk assessment combining medical, biopsychosocial and functional risk scores has the potential to optimize site-of-care decisions and thus allocation of limited health-care resources. The aim of this factorial design study is twofold: first, for Intervention A, it investigates antibiotic exposure of patients treated with a protocol based on the type of UTI, procalcitonin (PCT) and pyuria. Second, for Intervention B, it investigates the usefulness of the prognostic biomarker proadrenomedullin (ProADM) integrated into an interdisciplinary assessment bundle for site-of-care decisions. Methods and design This randomized controlled open-label trial has a factorial design (2 × 2). Randomization of patients will be based on a pre-specified computer-generated randomization list and independent for the two interventions. Adults with UTI presenting to the emergency department (ED) will be screened and enrolled after providing informed consent. For our first Intervention (A), we developed a protocol based on previous observational research to recommend initiation and duration of antibiotic use based on the clinical presentation of UTI, pyuria and PCT levels. For our second intervention (B), an algorithm was developed to support site-of care decisions based on the prognostic marker ProADM and distinct nursing factors on days 1 and 3. Both interventions will be compared with a control group conforming to the guidelines. The primary endpoints for the two interventions will be: (A) overall exposure to antibiotics and (B) length of physician-led hospitalization within a follow-up of 30 days. Endpoints are assessed at discharge from hospital, and 30 and 90 days after admission. We plan to screen 300 patients and enroll 250 for an anticipated estimated loss of follow-up of 20%. This will provide adequate power for the two interventions. Discussion This trial investigates two strategies for improved individualized medical care in patients with UTI. The minimally effective duration of antibiotic therapy is not known for UTIs, which is important for reducing the selection pressure for antibiotic resistance, costs and drug-related side effects. Triage decisions must be improved to reflect the true medical, biopsychosocial and functional risks in order to allocate patients to the most appropriate care setting and reduce hospital-acquired disability. Trial registration Trial registration number:ISRCTN13663741