Benign recurrent lymphocytic meningitis (Mollaret's meningitis) in Denmark: a nationwide cohort study.

BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

Viral lumbosacral radiculitis (Elsberg syndrome) in Denmark.

PURPOSE: To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). METHODS: Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. RESULTS: Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27-43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31-514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). CONCLUSIONS: Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.

Clinical features and prognostic factors in adults with viral meningitis.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

The ratio of neutrophil-to-lymphocyte and platelet-to-lymphocyte and association with mortality in community-acquired pneumonia: a derivation-validation cohort study.

RATIONALE: The ratio of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and platelet-to-lymphocyte (PLR) are biomarkers that have shown potential for predicting mortality in several diseases. For patients hospitalized with community-acquired pneumonia (CAP), the prognostic capabilities of these biomarkers are unknown. OBJECTIVE: Investigate whether NLR, MLR or PLR were associated with 90-day mortality in CAP. Further, investigate whether the prediction rule CURB-65 could be improved by adding these biomarkers. METHODS: A derivation-validation study using a Danish multicentre retrospective cohort as the derivation cohort (N = 831) and a European multicentre prospective cohort as the validation cohort (N = 2463). Associations between biomarkers and mortality were assessed using Cox proportional hazard models with adjustments for sex, CURB-65 and comorbidities. A cut-off value for biomarkers was determined using Youden's J Statistics. The performance of CURB-65 with added biomarkers was evaluated using receiver-operating characteristics. RESULTS: In both cohorts increasing NLR and PLR were associated with 90-day mortality. In the derivation cohort, the hazard ratios for NLR and PLR were 1.016 (95% confidence interval (CI) 1.001-1.032, P = 0.038) and 1.001 (95% CI 1.000-1.001, P = 0.035), respectively. Adding these biomarkers to CURB-65 did not improve its performance. CONCLUSIONS: NLR and PLR were associated with 90-day mortality in CAP, but did not improve CURB-65.

Risk Factors and Prognosis of Epilepsy Following Brain Abscess: A Nationwide Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Epilepsy in patients with brain abscess is frequent, but risk factors and prognosis remain undetermined. This study examined risk factors of epilepsy among survivors of brain abscess and associated prognosis. METHODS: Nationwide, population-based healthcare registries were used to compute cumulative incidences and cause-specific adjusted hazard rate ratios (adj. HRRs) with 95% CIs for epilepsy among 30-day survivors of brain abscess from 1982 through 2016. Data were enriched with clinical details by medical record review of patients hospitalized from 2007 through 2016. Adjusted mortality rate ratios (adj. MRRs) were examined using epilepsy as a time-dependent variable. RESULTS: The study included 1,179 30-day survivors of brain abscess among whom 323 (27%) developed new-onset epilepsy after a median of 0.76 years (interquartile range [IQR] 0.24-2.41). At admission for brain abscess, the median age was 46 years (IQR 32-59) in patients with epilepsy compared with 52 years (IQR 33-64) in those without epilepsy. The proportion of female individuals was similar in patients with and without epilepsy (37%). Adj. HRRs for epilepsy were 2.44 (95% CI 1.89-3.15) for aspiration or excision of brain abscess, 2.37 (1.56-3.60) for alcohol abuse, 1.75 (1.27-2.40) for previous neurosurgery or head trauma, 1.62 (1.17-2.25) for stroke, and 1.55 (1.04-2.32) for age group 20-39 years. Cumulative incidences were increased in patients with alcohol abuse (52% vs 31%), aspiration or excision of brain abscess (41% vs 20%), previous neurosurgery or head trauma (41% vs 31%), and stroke (46% vs 31%). Analysis using clinical details from medical record review of patients from 2007 through 2016 demonstrated adj. HRRs of 3.70 (2.24-6.13) for seizures at admission for brain abscess and 1.80 (1.04-3.11) for frontal lobe abscess. By contrast, adj. HRR was 0.42 (0.21-0.86) for occipital lobe abscess. Using the entire registry-based cohort, patients with epilepsy had an adj. MRR of 1.26 (1.01-1.57). DISCUSSION: Important risk factors of epilepsy were seizures during admission for brain abscess, neurosurgery, alcoholism, frontal lobe abscess, and stroke. Epilepsy was associated with an increased mortality. Antiepileptic treatment may be guided by individual risk profiles, and a specialized follow-up is highlighted by an increased mortality in survivors with epilepsy.

Clinical features and prognostic factors in adults with brain abscess.

Studies on brain abscess are hampered by single-centre design with limited sample size and incomplete follow-up. Thus, robust analyses on clinical prognostic factors remain scarce. This Danish nationwide, population-based cohort study included clinical details of all adults (≥18 years) diagnosed with brain abscess in the Danish National Patient Registry from 2007 through 2014 and the prospective clinical database of the Danish Study Group of Infections of the Brain covering all Danish departments of infectious diseases from 2015 through 2020. All patients were followed for 6 months after discharge. Prognostic factors for mortality at 6 months after discharge were examined by adjusted modified Poisson regression to compute relative risks with 95% confidence intervals (CI). Among 485 identified cases, the median age was 59 years [interquartile range (IQR 48-67)] and 167 (34%) were female. The incidence of brain abscess increased from 0.4 in 2007 to 0.8 per 100 000 adults in 2020. Immuno-compromise was prevalent in 192/485 (40%) and the clinical presentation was predominated by neurological deficits 396/485 (82%), headache 270/411 (66%), and fever 208/382 (54%). The median time from admission until first brain imaging was 4.8 h (IQR 1.4-27). Underlying conditions included dental infections 91/485 (19%) and ear, nose and throat infections 67/485 (14%), and the most frequent pathogens were oral cavity bacteria (59%), Staphylococcus aureus (6%), and Enterobacteriaceae (3%). Neurosurgical interventions comprised aspiration 356/485 (73%) or excision 7/485 (1%) and was preceded by antibiotics in 377/459 (82%). Fatal outcome increased from 29/485 (6%) at discharge to 56/485 (12%) 6 months thereafter. Adjusted relative risks for mortality at 6 months after discharge was 3.48 (95% CI 1.92-6.34) for intraventricular rupture, 2.84 (95% CI 1.45-5.56) for immunocompromise, 2.18 (95% CI 1.21-3.91) for age >65 years, 1.81 (95% CI 1.00-3.28) for abscess diameter >3 cm, and 0.31 (95% CI 0.16-0.61) for oral cavity bacteria as causative pathogen. Sex, neurosurgical treatment, antibiotics before neurosurgery, and corticosteroids were not associated with mortality. This study suggests that prevention of rupture of brain abscess is crucial. Yet, antibiotics may be withheld until neurosurgery, if planned within a reasonable time period (e.g. 24 h), in some clinically stable patients. Adjunctive corticosteroids for symptomatic perifocal brain oedema was not associated with increased mortality.

Enterovirus Meningitis in Adults: A Prospective Nationwide Population-Based Cohort Study.

OBJECTIVE: To test the hypothesis that enterovirus meningitis (EM) is a frequent and self-limiting condition, the epidemiology of EM in adults was examined. METHODS: Using a prospective, nationwide, population-based database, all adults with EM confirmed by PCR of the CSF from 2015 to 2019 were included. Unfavorable outcome was defined as Glasgow Outcome Scale scores of 1-4 at discharge. Modified Poisson regression was used to compute adjusted relative risks (RRs). RESULTS: A total of 419 cases of EM in 418 adults (46% female, median age 31 years [interquartile range (IQR) 27-35]) yielded an incidence of 1.80/100,000/year. Admission diagnoses included CNS infection 247/397 (62%), other neurologic conditions 89/397 (22%), and cerebrovascular diseases 33/397 (8%). Genotype was available for 271 cases, of which echovirus 30 accounted for 155 (57%). Patients presented with headache 412/415 (99%), history of fever 303/372 (81%), photophobia 292/379 (77%), and neck stiffness 159/407 (39%). Fever (≥38.0°C) was observed in 192/399 (48%) at admission. The median CSF leukocyte count was 130 106/L (range 0-2,100) with polymorphonuclear predominance (>50%) in 110/396 (28%). Cranial imaging preceded lumbar puncture in 127/417 (30%) and was associated with non-CNS infection admission diagnoses and delayed lumbar puncture (median 4.8 hours [IQR 3.4-7.9] vs 1.5 [IQR 0.8-2.8], p < 0.001). Unfavorable outcome occurred in 99/419 (24%) at discharge; more often in female patients (RR 2.30 [1.58-3.33]) and less frequent in echovirus 30 (RR 0.67 [0.46-1.00]) in adjusted analyses. Outcome remained unfavorable in 22/379 (6%) after 6 months. CONCLUSIONS: EM is common among young, healthy adults. Although the long-term prognosis remains reassuring, a substantial proportion have moderate disability at discharge, especially female patients.

Do-not-resuscitate orders in patients with community-acquired pneumonia: a retrospective study.

BACKGROUND: To investigate the use of do-not-resuscitate (DNR) orders in patients hospitalized with community-acquired pneumonia (CAP) and the association with mortality. METHODS: We assembled a cohort of 1317 adults hospitalized with radiographically confirmed CAP in three Danish hospitals. Patients were grouped into no DNR order, early DNR order (≤48 h after admission), and late DNR order (> 48 h after admission). We tested for associations between a DNR order and mortality using a cox proportional hazard model adjusted for patient and disease related factors. RESULTS: Among 1317 patients 177 (13%) patients received a DNR order: 107 (8%) early and 70 (5%) late, during admission. Patients with a DNR order were older (82 years vs. 70 years, p < 0.001), more frequently nursing home residents (41% vs. 6%, p < 0.001) and had more comorbidities (one or more comorbidities: 73% vs. 59%, p < 0.001). The 30-day mortality was 62% and 4% in patients with and without a DNR order, respectively. DNR orders were associated with increased risk of 30-day mortality after adjustment for age, nursing home residency and comorbidities. The association was modified by the CURB-65 score Hazard ratio (HR) 39.3 (95% CI 13.9-110.6), HR 24.0 (95% CI 11.9-48,3) and HR 9.4 (95% CI: 4.7-18.6) for CURB-65 score 0-1, 2 and 3-5, respectively. CONCLUSION: In this representative Danish cohort, 13% of patients hospitalized with CAP received a DNR order. DNR orders were associated with higher mortality after adjustment for clinical risk factors. Thus, we encourage researcher to take DNR orders into account as potential confounder when reporting CAP associated mortality.

Hutchinson's sign of ophthalmic zoster.

A 77-year-old woman presented with ophthalmic zoster and nasal tip involvement, consistent with Hutchinson's sign. Ocular examination disclosed a swollen upper eyelid, chemosis, conjunctival injection, pus, and mild corneal endothelial decompensation. The presence of Hutchinson's sign requires urgent consultation with an ophthalmologist due to the high risk of ocular complications.

The Glycemic Gap and 90-Day Mortality in Community-acquired Pneumonia. A Prospective Cohort Study.

Rationale: Hyperglycemia is associated with mortality in patients with community-acquired pneumonia (CAP), and hyperglycemia may be a biomarker of severity. However, hyperglycemia has a major disadvantage because the association is diminished in patients with diabetes mellitus (DM). This hampers the use of hyperglycemia as a biomarker. Accounting for habitual glucose levels could overcome this disadvantage.Objectives: We hypothesized that the glycemic gap (the difference between plasma glucose and the estimated average glucose) may be associated with mortality irrespective of DM.Methods: Among 1,933 adults with CAP included in a prospective multicenter cohort, we investigated the association between the glycemic gap and 90-day mortality. Hemoglobin A1c was used to estimate the average glucose. The association was assessed with Cox proportional hazard models after adjustment for age, sex, CURB-65 (Confusion, urea >7 mmol/L, respiratory rate ≥30 breaths/minute, systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥65 years), and comorbidities. In the prespecified analysis the absolute and relative glycemic gaps were used as a continuous variable. In a post hoc analysis, the absolute and relative glycemic gaps were used as a categorical variable grouped according to quartiles.Results: In the post hoc analysis, patients with the lowest (negative) and highest (positive) absolute glycemic gap quartiles had increased risk of 90-day mortality (hazard ratio, 2.6; 95% confidence interval, 1.02-6.65; and hazard ratio, 2.5; 95% confidence interval, 1.01-6.06, respectively). A similar association was found for the relative glycemic gap. The associations were independent of age, CURB-65 score, sex, or number of comorbidities and not modified by DM.Conclusions: Patients with the highest and lowest glycemic gap may have an increased risk of 90-day mortality, and the association was not modified by DM. These associations were found in an exploratory post hoc analysis and should be validated in other populations before further conclusions can be made.

The inflamed sputum in lower respiratory tract infection: l-lactate levels are correlated to neutrophil accumulation.

Lower respiratory tract infections (LRTI) are common, but little is known about the response of biomarkers of inflammation in the lungs. Therefore, our primary aim was to compare the concentration of l-lactate to the concentration of neutrophils in sputum and systemic markers of infection. Because it is difficult to differentiate viral and bacterial infection on the basis of clinical presentation in LRTI, our secondary aim was to evaluate if l- and d-lactate may serve as markers of local inflammation as representatives of neutrophils and bacteria, respectively. METHODS: Patients with acute LRTI were prospectively recruited. Sputum samples were collected and analysed for neutrophil count, l-lactate and d-lactate. We had data on pathogens from sputum cultures and polymerase chain reaction (PCR) (atypical bacteria, virus) and C-reactive protein (CRP) from blood. RESULTS: In 44 sputum samples from 32 patients, the median (interquartile range (IQR)) sputum neutrophil granulocyte count was 0.615 × 107  cells/mL (0.236-1.575). The sputum neutrophil granulocyte count was associated with sputum l-lactate (p = 0.011) and CRP (p = 0.018), but not with d-lactate (p = 0.177). There was a strong association between sputum d-lactate and l-lactate (p < 0.0001). CONCLUSION: As l-lactate in sputum is closely correlated to sequestration of neutrophils in the lungs, l-lactate is a marker for local inflammation in LRTI and a potential biomarker in clinical management of LRTI. On expectorated sputum, d-lactate had no clinical relevance.

Associations between biomarkers at discharge and co-morbidities and risk of readmission after community-acquired pneumonia: a retrospective cohort study.

To investigate whether hemoglobin, white blood cell count (WBC), urea, sodium, albumin, and C-reactive protein at discharge in patients hospitalized for community-acquired pneumonia (CAP) are associated with 30-day readmission. This study is a retrospective cohort study, which included all adult patients discharged after hospitalization for CAP from three Danish hospitals between January 2011 and July 2012. The outcome was all-cause, unplanned, 30-day readmission. Biomarker concentrations at discharge were transformed into binary variables by using either upper or lower quartiles as cut-off; the upper quartile was used for WBC, urea, and C-reactive protein, and the lower quartile was used for hemoglobin, sodium, and albumin. The study population consisted of 1149 patients. One hundred eighty-four (16.0%) patients were readmitted. Independent risk factors of readmission were WBC ≥ 10.6 cells × 109/L (hazard ratio 1.50; 95% CI, 1.07-2.11) and albumin <32 g/L (hazard ratio 1.78; 95% CI, 1.24-2.54) at discharge and the presence of ≥ 2 co-morbidities (hazard ratio 1.74; 95% CI, 1.15-2.64). When WBC, albumin, and co-morbidities were combined into a risk-stratification tool, there was a step-wise increase in risk of readmission for patients with 1, 2, or 3 risk factors with hazard ratios of 1.76 (95% CI, 1.25-2.49), 2.59 (95% CI, 1.71-3.93), and 6.15 (95% CI 3.33-11.38), respectively. WBC ≥ 10.6 cells × 109/L and albumin < 32 g/L at discharge and the presence of ≥ 2 co-morbidities were independently associated with increased risk of 30-day readmission.

Undiagnosed Diabetes Mellitus in Community-Acquired Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diabetes mellitus is an important risk factor for community-acquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patients with community-acquired pneumonia is largely unknown. We aimed to determine the prevalence of prediabetes, undiagnosed diabetes mellitus, and risk factors associated with undiagnosed diabetes mellitus in a large European community-acquired pneumonia cohort. METHODS: This was a multicenter prospective cohort study of hospitals and private practices in Germany and Austria encompassing 1961 adults with community-acquired pneumonia included in the German Community-Acquired Pneumonia Competence Network (CAPNETZ) study between 2007 and 2014. The prevalence of undiagnosed diabetes mellitus and prediabetes was estimated based on hemoglobin A1c measurements. Logistic regression was used to assess risk factors for undiagnosed diabetes mellitus. RESULTS: Fifteen percent of patients had known diabetes mellitus. Among patients without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes. Male sex (odds ratio [OR], 2.45 [95% confidence interval {CI}, 1.35-4.45]), body mass index ≥25 kg/m2 (OR, 2.64 [95% CI, 1.48-4.72]), and hyperglycemia at admission (6-11 mM: OR, 2.93 [95% CI, 1.54-5.60] and ≥11 mM: OR, 44.76 [95% CI, 17.58-113.98]) were associated with undiagnosed diabetes mellitus. Patients with undiagnosed diabetes mellitus had a higher 180-day mortality rate compared to patients without diabetes mellitus (12.1% vs 3.8%, respectively; P = .001). CONCLUSIONS: Undiagnosed diabetes mellitus was prevalent among community-acquired pneumonia. Male sex, overweight, and hyperglycemia at admission were associated with undiagnosed diabetes mellitus. The long-term mortality among patients with undiagnosed diabetes mellitus was high compared to patients without diabetes mellitus.

Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark: a retrospective cohort study.

BACKGROUND: Community-acquired pneumonia (CAP) is a severe infection, with high mortality. Antibiotic strategies for CAP differ across Europe. The objective of the study was to describe the epidemiology of CAP in Denmark and evaluate the prognosis of patients empirically treated with penicillin-G/V monotherapy. METHODS: Retrospective cohort study including hospitalized patients with x-ray confirmed CAP. We calculated the population-based incidence, reviewed types of empiric antibiotics and duration of antibiotic treatment. We evaluated the association between mortality and treatment with empiric penicillin-G/V using logistic regression analysis. RESULTS: We included 1320 patients. The incidence of hospitalized CAP was 3.1/1000 inhabitants. Median age was 71 years (IQR; 58-81) and in-hospital mortality was 8%. Median duration of antibiotic treatment was 10 days (IQR; 8-12). In total 45% were treated with penicillin-G/V as empiric monotherapy and they did not have a higher mortality compared to patients treated with broader-spectrum antibiotics (OR 0.92, CI 95% 0.55-1.53). CONCLUSION: The duration of treatment exceeded recommendations in European guidelines. Empiric monotherapy with penicillin-G/V was commonly used and not associated with increased mortality in patients with mild to moderate pneumonia. Our results are in agreement with current conservative antibiotic strategy as outlined in the Danish guidelines.

Failure of CRP decline within three days of hospitalization is associated with poor prognosis of Community-acquired Pneumonia.

BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to monitor the patient's response during treatment in infectious diseases. Mortality from Community-acquired Pneumonia (CAP) remains high, particularly in hospitalized patients. Better risk prediction during hospitalization could improve management and ultimately reduce mortality levels. The aim of this study was to evaluate CRP on the 3rd day (CRP3) of hospitalization as a predictor for 30 days mortality. METHODS: A retrospective multicentre cohort study of adult patients admitted with CAP at three Danish hospitals. Predictive associations of CRP3 (absolute levels and relative decline) and 30 days mortality were analysed using receiver operating characteristics and logistic regression. RESULTS: Eight hundred and fourteen patients were included and 90 (11%) died within 30 days. The area under the curve for CRP3 level and decline for predicting 30 days mortality were 0.64 (0.57-0.70) and 0.71 (0.65-0.76). Risk of death was increased in patients with CRP3 level >75 mg/l (OR 2.44; 95%CI 1.36-4.37) and in patients with a CRP3 decline <50% (OR 4.25; 95%CI 2.30-7.83). In the multivariate analysis, the highest mortality risk was seen in patients who failed to decline by 50%, irrespective of the actual level of CRP (OR 7.8; 95%CI 3.2-19.3). Mortality risk increased significantly according to CRP decline for all strata of CURB-65 score. CONCLUSIONS: CRP responses day 3 is a valuable predictor of 30 days mortality in hospitalized CAP patients. Failure to decline in CRP was associated with a poor prognosis irrespective of the actual level of CRP or CURB-65.