Prediction model for pneumonia in primary care patients with an acute respiratory tract infection: role of symptoms, signs, and biomarkers.

BACKGROUND: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care. METHODS: From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model. RESULTS: Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (- 4%); however, CRP helped guidance of the decision which patients should be given antibiotics. CONCLUSIONS: Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners.

Prognostic value of pro-adrenomedullin, procalcitonin and C-reactive protein in predicting outcome of febrile urinary tract infection.

Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course that is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leucocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicated course of disease, a new biomarker-plasma midregional pro-adrenomedullin (MR-proADM)-was evaluated in patients with f UTI. We conducted a prospective multicentre cohort study including consecutive patients with f UTI at 35 primary-care centres and eight emergency departments. Clinical and microbiological data were collected and plasma biomarker levels were measured at presentation to the physician. Survival was assessed after 30 days. Of 494 fUTI patients, median age was 67 (interquartile range 49-78) years, 40% were male; two-thirds of them had significant co-existing medical conditions. Median MR-proADM level was 1.42 (interquartile range 0.67-1.57) nM; significantly elevated MR-proADM levels were measured in patients with bacteraemia, those admitted to the intensive care unit, and in 30-day and 90-day non-survivors, compared with patients without these characteristics. The diagnostic accuracy for predicting 30-day mortality in fUTI, reflected by the area-under-the-curve of receiver operating characteristics were: MR-proADM 0.83 (95% CI 0.71-0.94), PCT 0.71 (95% CI 0.56-0.85); whereas CRP, ESR and leucocyte count lacked diagnostic value in this respect. This study shows that MR-proADM assessed on first contact predicts a complicated course of disease and 30-day mortality in patients with fUTI and in this respect has a higher discriminating accuracy than the currently available biomarkers ESR, CRP, PCT and leucocyte count.

Predicting the need for radiologic imaging in adults with febrile urinary tract infection.

BACKGROUND: Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. METHODS: We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as "clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. RESULTS: Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH ≥7.0, and/or renal insufficiency (estimated glomerular filtration rate, ≤40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. CONCLUSIONS: Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule.

Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment.

OBJECTIVE: Home-based treatment of acute pyelonephritis (AP) is generally reserved for young non-pregnant women who lack co-morbidity. This study, focusing on the elderly and patients with co-morbidity, evaluates the Dutch primary care guideline that recommends referral to hospital only in case of suspected deterioration to severe sepsis or failure of antibiotic treatment, irrespective of patient's age, sex or co-morbidity. METHODS: A prospective observational cohort study including consecutive non-pregnant adults with AP. Clinical and microbiological outcome measures of non-referred patients from 35 primary health care centres (PHC) were compared to patients referred to two affiliating emergency departments (EDs). RESULTS: Of 395 evaluable patients, 153 were treated by PHCs and 242 referred to EDs. The median age was 63years [IQR 43-77], 34% were male, 58% had co-morbidity; all comparable between the PHC and ED group. Referred ED patients were more likely to have signs of sepsis and to have been pre-treated with antibiotics. Bacteraemia was present in 10% of patients in the PHC group and 27% in the ED group (RR 2.83; 95% CI: 1.64-4.86, p<0.001). Eight (5%) PHC patients were admitted during outpatient treatment but otherwise no major complications occurred. Clinical failure rates at 30days were similar between PHC patients and ED patients; 9% and 10% respectively. Mortality rates of PHC patients versus ED patients were 1% versus 5% at 30days (p=0.058) and 1% versus 7% at 90days (p=0.007). Complicated outcome occurred in 6% of the PHC patients versus 12% in the patients referred to ED (p=0.067). CONCLUSION: In a health care system with a well-organized primary care system and clear guideline, the outcome of adults with acute pyelonephritis, including men, the elderly and patients with co-morbidity, selected for oral antibiotic treatment at home did not lead to major complications.

[Churg-Strauss syndrome in a patient with asthma treated with montelukast]. / Syndroom van Churg-Strauss bij een astmapatiënt onder behandeling met montelukast.

A 75-year-old woman with a history of asthma, rhinitis and nasal polyps was admitted due to petechial lesions on the lower left leg and weakness of the right foot. Six weeks prior to admission, she had started treatment with montelukast 10 mg daily. Based on the asthma, eosinophilia, mononeuritis of the right leg and a skin biopsy showing small vessel vasculitis with eosinophilic granulocytes, the patient was diagnosed with Churg-Strauss syndrome (CSS). After consulting with the pulmonologist, montelukast therapy was discontinued and replaced with a combined preparation of a parasympatholytic and a P2-sympathomimetic. The patient was also given prednisone 60 mg daily, which resulted in prompt clinical improvement and resolution of the eosinophilia. Development of CSS has been associated with the use of montelukast and should be considered in patients with asthma who develop new symptoms, such as neuritis, vasculitis of the skin or pulmonary infiltrates with an increase in eosinophilia during montelukast therapy. In these patients, treatment with montelukast should be discontinued, although whether a causal relationship exists between montelukast and CSS continues to be debated in the literature.

[Invasive zygomycosis: notably in diabetes mellitus and iron overload]. / Invasieve zygomycose: vooral bij diabetes mellitus en ijzerstapeling.

The incidence of invasive zygomycosis, a severe and often life-threatening infection, is increasing. The most common manifestations are pulmonary infection (following anti-cancer chemotherapy or haematopoietic stem-cell transplant) and invasive rhinocerebral infection (in patients with diabetes mellitus or iron overload). Iron metabolism plays an important role in the pathogenesis of infection in these high-risk populations. Rapid diagnosis, reversal of the underlying predisposition and timely surgical debridement are the underlying principles of therapy for this disease.

Meningitis caused by Capnocytophaga canimorsus: when to expect the unexpected.

In this article we review the available data concerning meningitis caused by Capnocytophaga canimorsus. The clinical presentation of this rare condition is described with the emphasis on associated conditions and management issues. Two additional cases, illustrating the difficulties in recognizing this rare disease, are presented. Reviewing a total of 28 reported cases, a preceding bite-incident by a cat or dog, or close contact with these animals, was described in the majority of cases (89%). Patients had a median age of 58 years; splenectomy and alcohol abuse were noted in, respectively, 18% and 25% of patients. Only in one case immune suppressive drug use was reported. The diagnosis C. canimorsus meningitis should be considered in healthy and immunocompromised adults, especially after splenectomy, who present with symptoms attributable to meningitis and a history of recent exposure to dogs or cats. The possibility of this condition has implications for both the diagnostic work-up and the treatment of the patient.

Successful treatment of fungus balls due to fluconazole-resistant Candida sake obstructing ureter stents in a renal transplant patient.

Reported here is the case of a 72-year-old renal transplant recipient with stenosis of the neo-ureter requiring stents, who was admitted to hospital with pyonephrosis caused by fungus balls. Fluconazole-resistant Candida sake was grown. Treatment with external drainage of the renal pelvis and intravenous and local administration of caspofungin resulted in relief of the obstruction. Eradication of the infection was achieved by surgical removal of the ureter with all stents and construction of a cysto-pyelostomy.

Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands.

OBJECTIVE: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands. METHODS: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens. RESULTS: With voriconazole, the mean cost for treating invasive aspergillosis per patient was E32 651 (2.5th percentile and 97.5th of uncertainty distribution: E30 037; E36 859), compared to E33 616 (E30 920; E39 633) for conventional amphotericin B and E29 115 (E23 537; E61 414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was E150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%. CONCLUSION: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.

Changing epidemiology of melioidosis? A case of acute pulmonary melioidosis with fatal outcome imported from Brazil.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei. It is endemic in South East Asia and tropical regions of Northern Australia. Sporadic cases have been described elsewhere. In this article we present a case of acute pulmonary melioidosis with fatal outcome imported from Brazil. The most common pathogen causing severe community-acquired pneumonia in Brazil is Streptococcus pneumoniae. Other possible pathogens include Legionella spp., Mycoplasma pneumonia, Gram-negative rods and viruses. There are few reports of melioidosis in the Americas. This article represents the second known human case of melioidosis from Brazil. Recognition of melioidosis as a possible cause of severe pneumonia, even if a patient has not been travelling in a highly endemic area, is important because of the therapeutic consequences. The epidemiology of melioidosis will be reviewed.

[A focus on incidents and patient communication skills in the training of internists]. / Aandacht voor incidenten en communicatie met patiënten in de opleiding tot internist.

Development of communication skills is an important aspect of the training of young physicians. In our hospital, we have developed a programme consisting of monthly 1-hour meetings in which the residents in internal medicine discuss incidents and communication problems with patients or their relatives. During these meetings, residents give feedback to each other under the supervision of the consultation-liaison psychiatrist. Important issues that have been discussed include refusal of treatment by patients, how to handle aggression, how to respond to complaints, relating bad news to patients, euthanasia, and dealing with personal problems or work-related stress. The meeting is well attended and appreciated by the residents. We believe that this approach of improving communication skills based on actual problems encountered in daily practice makes a valuable contribution to the training of young doctors.

Chills in 'early sepsis': good for you?

We evaluated the predictive value of chills, bacteraemia and endotoxaemia for in-hospital mortality and survival at 5-10 years long-term follow-up in a prospective cohort of 'early sepsis' patients presenting with fever resulting from community-acquired pneumonia or pyelonephritis. Febrile patients with chills had bacteraemia more often (RR 3.1, 95% CI 1.8-5.4) than those without chills. Neither chills nor bacteraemia were significantly related to in-hospital mortality, but patients with endotoxaemia had a higher in-hospital mortality rate than those without endotoxaemia. Patients with chills had a significantly higher survival rate at long-term follow-up than those without chills on admission: the estimated risk of dying was 0.644 (95% CI 0.43-0.95, P = 0.029) for an individual with chills, compared to a person without chills, adjusting for the other factors [age cohort, underlying disease and the pro-inflammatory response in the blood, i.e. tumour necrosis factor-alpha (TNF-alpha) and blood leucocyte number, as scored on hospital admission] in the Cox proportional hazards model. Chills may characterize a patient subpopulation that upon pulmonary and urinary tract infection is able to raise a more rapid and/or efficient host response.

[New developments in antifungal therapy: fluconazole, itraconazole, voriconazole, caspofungin]. / Nieuwe ontwikkelingen in de antifungale therapie: fluconazol, itraconazol, voriconazol, caspofungine.

The azole antifungal voriconazole and the echinocandin caspofungin have recently become available for the treatment of invasive mycoses. Fluconazole remains the drug of choice for candidemia, except for infections with one of the resistent species such as Candida krusei and some strains of Candida glabrata. In these cases, as well as in patients who cannot tolerate azoles in connection with side effects or drug interactions, caspofungin is an attractive alternative. Voriconazole has become the drug of choice for severe invasive aspergillosis. Itraconazole is a good alternative for milder and chronic forms of aspergillosis. The use of conventional amphotericin B will be limited by the availability of the new drugs. In view of their high costs, the lipid-bound forms of amphotericin B will usually be given only as salvage therapy in case of failure, in patients who are unable to tolerate either conventional amphotericin or one of the newer agents, and for the treatment of zygomycosis.

Plasma secretory leukocyte protease inhibitor in febrile patients.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) forms an integral part of the lung's defence, by its antimicrobial activity and by its ability to neutralize serine proteases that are released by granulocytes into the inflammatory exudate. Here, we investigate in febrile patients admitted to hospital whether plasma SLPI can serve as a marker of lung infection. METHODS: We prospectively determined the SLPI concentration in 152 febrile patients (median 73 [inter-quantile range (IQR): 58-82] year; 50% male) admitted to hospital because of infection of the airways (n = 44) or pneumonia (n = 108; i.e. consolidation on chest X-ray), and in 48 febrile patients (78 [IQR: 71-85] year; 52% male) admitted because of pyelonephritis, as well as afebrile age-matched controls (n = 38). In addition, erythrocyte sedimentation rate (ESR), peripheral blood leukocytes, plasma TNFalpha and IL-10, and parameters of the APACHE-II score were determined on admission. RESULTS: In febrile patients, SLPI was significantly increased (P < 0.001) compared with afebrile controls (63 [IQR: 50-76] ng/mL): plasma SLPI (113 [IQR: 83-176] ng/mL) was highest (P < 0.005) in patients with pneumonia compared with other groups (88 [IQR: 70-118] ng/mL). Only in patients with pneumonia, bacteremia significantly increased (P < 0.01) SLPI concentrations. Using a radiological classification of pulmonary infiltrates based on their size, it was found that plasma SLPI was proportional to the extent of lung tissue involved: the median concentration increased from 95 [IQR: 74-139] ng/mL in unilateral segmental consolidation up to 271 [IQR: 180-460] ng/mL in bilateral lobar consolidations. In a multivariate analysis, the association between SLPI and extent of consolidation was about two-fold stronger than, and independent of, the association between SLPI and erythrocyte sedimentation rate, TNFalpha, and parameters of the composite APACHE-II score, such as heart rate and blood pressure, that reflect severity of illness. CONCLUSION: SLPI is an indicator of the presence and extent of pneumonia in febrile patients admitted to hospital. In patients with an infection with its primary source located outside the lung, plasma SLPI likely reflects the mucosal response to circulating inflammatory mediators reflecting severity of illness.

[Two patients with fever, chills and pain in the right upper abdominal quadrant accompanied by hyperbilirubinaemia: pylephlebitis]. / Twee patiënten met koorts, koude rillingen en pijn rechts in de bovenbuik en hyperbilirubinemie: pyleflebitis.

Two male patients aged 55 and 77 years, respectively, presented to the casualty department with fever, chills and right abdominal upper quadrant tenderness. They also had hyperbilirubinaemia. Based on CT scan findings and blood cultures yielding Bacteroides fragilis, a diagnosis of pylephlebitis (septic thrombophlebitis of the mesenteric veins and/or the portal vein) was made. This is a condition with a mortality rate of 10-70%. Primary sources such as diverticulitis are often seen in patients with pylephlebitis, in which bacteria are drained by the mesenteric veins and cause a thrombus in the portal system. In the two patients no primary focus was detected. They were treated with intravenous antibiotic therapy followed by oral antibiotics, and were discharged in good health. Pylephlebitis can be complicated by liver abscesses. Treatment consists of broad-spectrum antibiotics which are adjusted based on the blood cultures results. The duration of treatment is between two and six weeks, depending on the presence of liver abscesses. In patients with abscesses that cannot be drained, longer treatment may be indicated.

[Predictive value of chills in patients presenting with fever to urgent care department]. / De betekenis van een koude rilling bij patiënten met koorts op de spoedeisende-eerstehulpafdeling.

OBJECTIVE: To ascertain the correlation between chills, bacteraemia, infection type and clinical progress in patients presenting with fever to the casualty department. DESIGN: Prospective, descriptive. METHOD: Anamnestic, clinical and microbiological data were registered from patients with fever (> 38.2 degrees C rectal) presenting to the Casualty Department of the Leiden University Hospital and the Bronovo Hospital, in the period 1 February 1994-31 July 1995 respectively 1 February 1996-31 July 1997. RESULTS: A total of 764 patients (424 men and 340 women; median age: 66 years) were included in the study. A chill was reported by 270 patients (35%). Bacteria were isolated from the blood culture in the case of 141 patients (18%). The relative risk (RR) for bacteraemia in the case of a chill was 2.8 (95% CI: 2.1-3.8); the positive predictive value of a chill for bacteraemia was 31% and the negative predictive value 89%. For 683 (89%) of the 764 patients the cause of the fever was probably or certainly an infection, which was mostly pulmonary (319 patients; 42%) or urogenital (112 patients; 15%) in origin. The positive predictive value was 24% for patients with respiratory tract infections and 48% for patients with urinary tract infections. Mortality occurred in the case of 62 patients (8%) after a median admission period of 11 days. The patients who died were older than the patients discharged (p < 0.01) and there was a statistically significant correlation between mortality with bacteraemia (RR: 1.1) and serious comorbidity (RR: 6.1). CONCLUSION: There was a strong correlation between the chill indicated in the anamnesis and bacteraemia, especially in patients with a urinary tract infection. Bacteraemia, advanced age and serious comorbidity were unfavourable prognostic factors.