Martin Krause

Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial

CONTEXTnIn previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).nnnOBJECTIVEnTo examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.nnnDESIGN, SETTING, AND PATIENTSnA multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.nnnINTERVENTIONnPatients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.nnnMAIN OUTCOME MEASURESnNoninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.nnnRESULTSnThe rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%).nnnCONCLUSIONnIn patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.nnnTRIAL REGISTRATIONnisrctn.org Identifier: ISRCTN95122877.

Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia : a prospective cohort trial

BACKGROUNDnGuidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia (CAP). However, the yield of true-positive results is low. We investigated the benefit of procalcitonin (PCT) on hospital admission to predict blood culture positivity in CAP.nnnMETHODSnThis was a prospective cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission.nnnRESULTSnA total of 73 (7.9%) patients had true bacteremia (43 of 463 in the derivation cohort, 30 of 462 in the validation cohort). The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar (derivation cohort, 0.83; 95% CI, 0.78-0.89; validation cohort, 0.79; 95% CI, 0.72-0.88). Overall, PCT was a significantly better predictor for blood culture positivity than WBC count, C-reactive protein, and other clinical parameters. In multivariate regression analysis, only antibiotic pretreatment (adjusted odds ratio, 0.25; P < .05) and PCT serum levels (adjusted odds ratio, 3.72; P < .001) were independent predictors. Overall, a PCT cutoff of 0.1 microg/L would enable reduction of the total number of blood cultures by 12.6% and still identify 99% of the positive blood cultures. Similarly, 0.25 microg/L and 0.5 microg/L cutoffs would enable reduction of blood cultures by 37% and 52%, respectively, and still identify 96% and 88%, respectively, of positive blood cultures.nnnCONCLUSIONSnInitial PCT level accurately predicted blood culture positivity in patients with CAP. PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources.

Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections

IntroductionMeasurement of prohormones representing different pathophysiological pathways could enhance risk stratification in patients with community-acquired pneumonia (CAP) and other lower respiratory tract infections (LRTI).MethodsWe assessed clinical parameters and five biomarkers, the precursor levels of adrenomedullin (ADM), endothelin-1 (ET1), atrial-natriuretic peptide (ANP), anti-diuretic hormone (copeptin), and procalcitonin in patients with LRTI and CAP enrolled in the multicenter ProHOSP study. We compared the prognostic accuracy of these biomarkers with the pneumonia severity index (PSI) and CURB65 (Confusion, Urea, Respiratory rate, Blood pressure, Age 65) score to predict serious complications defined as death, ICU admission and disease-specific complications using receiver operating curves (ROC) and reclassification methods.ResultsDuring the 30 days of follow-up, 134 serious complications occurred in 925 (14.5%) patients with CAP. Both PSI and CURB65 overestimated the observed mortality (X2 goodness of fit test: P = 0.003 and 0.01). ProADM or proET1 alone had stronger discriminatory powers than the PSI or CURB65 score or any of either score components to predict serious complications. Adding proADM alone (or all five biomarkers jointly) to the PSI and CURB65 scores, significantly increased the area under the curve (AUC) for PSI from 0.69 to 0.75, and for CURB65 from 0.66 to 0.73 (P < 0.001, for both scores). Reclassification methods also established highly significant improvement (P < 0.001) for models with biomarkers if clinical covariates were more flexibly adjusted for. The developed prediction models with biomarkers extrapolated well if evaluated in 434 patients with non-CAP LRTIs.ConclusionsFive biomarkers from distinct biologic pathways were strong and specific predictors for short-term adverse outcome and improved clinical risk scores in CAP and non-pneumonic LRTI. Intervention studies are warranted to show whether an improved risk prognostication with biomarkers translates into a better clinical management and superior allocation of health care resources.Trial RegistrationNCT00350987.

Diagnostic performance in a primary referral hospital assessed by autopsy: Evolution over a ten-year period

BACKGROUNDnDespite remarkable progress in modern laboratory testing and imaging technology in recent years, diagnostic errors still occur. To assess whether diagnostic performance in a primary referral hospital improves with new diagnostic tools and algorithms, autopsy reports were analyzed over a ten-year period to monitor diagnostic errors.nnnMETHODSnMedical reports from 1997 to 2006 were compared retrospectively with autopsy reports. A diagnostic error was assumed when the main clinical diagnosis was missed, independently of whether this influenced the patients survival or whether this error led to incorrect treatment without effect on survival. Two cardiovascular markers with high sensitivity, namely cardiac troponin T and D-dimer testing and two algorithms for thoracic pain and thromboembolic disease were introduced during the study period.nnnRESULTSn970 cases were included; the autopsy rate was 50.1%. Cardiovascular diseases were misdiagnosed in 18.7%, followed by infectious diseases in 12.9%, oncological 3.6% and neurological diseases in 1.8%. The most commonly missed diagnoses were myocardial infarction, pulmonary embolism and aortic dissection; however, the rate of errors for cardiovascular diseases decreased over the 10 years (p<0.002). Overall diagnostic sensitivity and specificity rose from 67% to 87% and from 94% to 99%, respectively.nnnCONCLUSIONnAutopsy remains a valuable tool to measure diagnostic performance. Errors occur most frequently in cardiovascular events, whereas in malignant and neurological diseases they are rare. The significant improvement of diagnostic accuracy for cardiovascular diseases is associated with the introduction of new sensitive laboratory tests and algorithms for thoracic pain and thromboembolic diseases.

Quality of care delivered by fee-for-service and DRG hospitals in Switzerland in patients with community-acquired pneumonia

PRINCIPLESnReimbursement 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.nnnMETHODSnThis 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).nnnRESULTSnLOS 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.nnnCONCLUSIONSnThis 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.

Invasive aspergillosis in non-neutropenic patients

Host defense against invasion of Aspergillus spp. relies on effective phagocytosis by neutrophils and macrophages [1]. Accordingly, surveillance mainly focuses on leukaemia patients receiving myeloablative therapies in which the risk for invasive aspergillosis (IA) starts to rise drastically after 10 days of neutropenia. However, IA is occasionally observed in non-neutropenic patients who have some underlying disease or who receive immunosuppressive therapy that does not impair neutrophil counts [2–5]. The mortality of these patients is still high due to the underlying conditions and due to the difficulties to recognize the fungal infection without invasive procedures [3]. Herein, we review the cases we found over a period of ten years who were treated in two non-university teaching hospitals in Eastern Switzerland serving a population of 250,000 and with a autopsy rate of approximately 50%. We reviewed all case records from patients in which Aspergillus was found in biopsy or autopsy specimens over a ten year period

Chronic lymphocytic leukaemia, dyspnoea and “tree-in-bud” sign on chest CT scan

Chronic lymphocytic leukaemia (CLL) is a common disorder. Patients typically present with lymphadenopathy, splenomegaly and marked lymphocytosis (often >100 000/&mgr;l). Although pulmonary involvement from CLL can be found in more than one third of patients on autopsy, respiratory symptoms caused by the disease itself are not often reported. Pulmonary involvement mainly includes parenchymal infiltrates, peribronchial and perivascular infiltration, recurrent bacterial pneumonia, oedema or infarction, pleural effusions, and lymphadenopathy. Occasionally, patients may present with dry cough and progressive dyspnoea, even with low peripheral white blood cell count. We report a case of CLL and dyspnoea at rest, predominant “tree-in-bud” sign on chest computed tomography scan, and biopsy proven bronchiolar infiltration with monoclonal lymphocytes. With bronchoalveolar lavage alone, the diagnosis would have been missed. Chemotherapy with rituximab, cyclophosphamide, and fludarabinphosphate led to a prompt clinical and radiological improvement with a gain in 6 min walking distance from 60 to 210 m.

A pneumonia leading to blindness

A 56-year-old man with oesophageal/pyloric stenosis after a suicide attempt with toilet detergent was treated with tazobactam/piperacillin followed by oral levofloxacin for aspiration pneumonia in the right lower field. Seven days later, bilateral chemosis and conjunctival hyperaemia developed (figure 1), followed by right eye blindness and reduced light perception in the left eye. A sinus thrombosis or sinusitis was excluded by CT scan. Diagnosis of bilateral endophthalmitis was made followed by left pars plana vitrectomy, intravitreal vancomycin/ceftazidime and parenteral cefepime application. Blood and vitreous cultures revealed Klebsiella pneumoniae …