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.

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.

[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.

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.

[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.

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.

Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993. An analysis of 78 cases.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) occurs in immunocompromised patients without the acquired immunodeficiency syndrome (AIDS). There has been an increasing yearly number of cases of PCP in our patients without AIDS. OBJECTIVE: To determine the nature of the underlying disorder and previous immunosuppressive treatment in patients with PCP without AIDS. METHOD: A study of the charts of 78 such patients admitted to our hospital from 1980 through 1993. RESULTS: The number of PCP cases per year increased during the period studied. All patients had an underlying disorder, either hematologic malignancy (49%), solid organ tumor (4%), vasculitis or other immunologic disorder (22%), or they had undergone renal transplantation (17%) or bone marrow transplantation (9%). Previous immunosuppressive medication consisted of prednisone or other corticosteroids in 72 (92%) of 78 patients, cytotoxic drugs in 55 (71%) of 78 patients, both in 50 (64%) of 78 patients, and none in one patient. Quantification of previous corticosteroid treatment showed a large variability among patients. The overall mortality rate for patients was 35% (27/78). Mortality was significantly higher in patients with a concomitant pulmonary infection (P = .01), an underlying disorder other than that which resulted in renal transplantation (P = .03), mechanical ventilation (P < .001), previous chemotherapy (P = .04), as well as previous cyclophosphamide treatment (P = .01). A trend toward a higher mortality in patients with previous corticosteroid use was detected (P = .06). CONCLUSION: Pneumocystis carinii pneumonia may complicate a variety of immunocompromised states, with considerable mortality. Pneumocystis carinii pneumonia occurred at all levels of immunosuppression; no threshold level could be defined.

[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.

Purpura fulminans and symmetrical peripheral gangrene caused by Capnocytophaga canimorsus (formerly DF-2) septicemia--a complication of dog bite.

We review the syndrome of Capnocytophaga canimorsus (DF-2) septicemia after exposure to dogs or cats. We describe a previously healthy patient who developed diffuse intravascular coagulation and symmetrical peripheral gangrene as a result of C. canimorsus septicemia after a dog bite. To our knowledge, this patient was the first to receive combined plasmapheresis and leukapheresis for C. canimorsus septicemia. Symmetrical peripheral gangrene is frequently associated with C. canimorsus septicemia and may lead to an early diagnosis in patients who become severely ill after a dog bite. Other complications include arthritis, meningitis, and endocarditis. These manifestations can also be found in previously healthy patients, although a prior splenectomy or other causes of impaired host defense clearly enhance the risk. Prompt treatment with penicillin G is required.

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.

Tenosynovitis due to Mycobacterium avium-intracellulare: case report and a review of the literature.

A 57-year-old female patient presented with a tenosynovitis due to Mycobacterium avium-intracellulare (MAI). A relapse occurred following surgical treatment, after which she was successfully treated with ansamycin and ethambutol. Previously reported cases of tenosynovitis due to MAI are reviewed and the treatment modalities are discussed.

Treatment of invasive aspergillosis with itraconazole in a patient with chronic granulomatous disease.

An 18-year-old boy with X-linked chronic granulomatous disease (CGD) developed Aspergillus fumigatus pneumonia and multifocal osteomyelitis. Treatment with amphotericin B resulted in only moderate improvement of the lesions and was accompanied by considerable toxicity. In contrast, administration of the new triazole drug itraconazole led to complete disappearance of all signs of infection. We conclude that itraconazole may be a valuable new drug for treating invasive aspergillosis in patients with CGD, although the duration of treatment remains to be established.

The efficacy of itraconazole against systemic fungal infections in neutropenic patients: a randomised comparative study with amphotericin B.

In a randomised clinical trial, we compared the efficacy of the new triazole drug itraconazole (200 mg orally twice daily) with that of amphotericin B (0.6 mg/kg daily or 0.3 mg/kg in combination with flucytosine) in neutropenic (less than 500 x 10(6)/l neutrophils) patients with proven or highly suspected systemic fungal infections. Patients with unexplained fever alone were not included in the study. Of the 40 patients enrolled, 32 patients (16 males, 16 females) were evaluable. Sixteen patients (median age 49 years) were treated with itraconazole for a median period of 20 days and 16 patients (median age 32 years) received amphotericin B for a median period of 13 days. The overall clinical response was 10/16 (63%) for patients treated with itraconazole and 9/16 (56%) for patients treated with amphotericin B (P greater than 0.90). Itraconazole seemed to be more effective against Aspergillus infections, whereas amphotericin B seemed to be more effective against candidal infections, although the differences were not statistically significant.

Mediastinal rupture of a thoracoabdominal mycotic aneurysm caused by Salmonella typhimurium in an immunocompromised patient.

A case is presented of rupture of a mycotic thoracoabdominal aneurysm caused by Salmonella typhimurium in a patient on immunosuppressive therapy following kidney transplantation. After initial medical treatment, surgery consisted of local debridement and implantation of an aortic prosthesis. Lifelong antibiotic treatment was prescribed because of the combination of immunosuppressive therapy, the history of recurrent S. typhimurium bacteremia and the presence of an aortic prosthesis.

No effect of recombinant human interleukin-1 on numbers of peripheral blood and peritoneal leukocytes during acute inflammation.

Recombinant human interleukin-1 (IL-1) can prolong the survival of mice with severe systemic bacterial or fungal infections. In order to assess whether this is due to an effect of IL-1 on the production of leukocytes or their migration to the site of infection, the influence of IL-1 on the influx of leukocytes to the site of an acute inflammation was studied in normal and in granulocytopenic mice. The numbers of granulocytes, lymphocytes, and monocytes or macrophages in both the circulation and the peritoneal cavity were determined during an acute sterile inflammation elicited by intraperitoneal injection of either newborn calf serum (NBCS) or heat-killed Candida albicans, and during a peritoneal infection with viable C. albicans. After normal mice were injected intraperitoneally with NBCS or 10(7) CFU heat-killed or viable C. albicans, the number of peritoneal granulocytes rose sharply within 6 h. Pretreatment of mice with a single intraperitoneal dose of 80 ng IL-1 24 h before injection of an inflammatory stimulus did not influence the course of the numbers of leukocytes in the circulation or in the peritoneal cavity. When mice were rendered granulocytopenic by cyclophosphamide, both the influx of granulocytes into the peritoneal cavity and the concomitant rise in the number of peripheral blood granulocytes after injection of NBCS, killed or viable C. albicans was virtually absent. Pretreatment of granulocytopenic mice with IL-1 did not influence the course of the numbers of leukocytes in either the circulation or the peritoneal cavity. These findings show that the beneficial effect of a single dose of IL-1 on the course of candidal infections in normal or granulocytopenic mice is not attributable to the influx of granulocytes or monocytes.

Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritoneal leukocytes in mice under normal conditions and during acute inflammatory reaction.

In order to develop a suitable model for studying the role of granulocytes and monocytes in resistance against pathogenic microorganisms, we investigated the effect of irradiation and cytostatic treatment (cyclophosphamide and VP-16) on the number of both peripheral blood and peritoneal leukocytes in male Swiss mice. Irradiation and cyclophosphamide treatment severely decreased the number of both granulocytes and monocytes in peripheral blood, whereas VP-16 only lowered the number of blood monocytes to a significant degree and had little effect on the number of blood granulocytes or lymphocytes. When normal mice were injected intraperitoneally with newborn calf serum (NBCS) the number of peritoneal granulocytes rose about 100-fold within 6 h. In irradiated and cyclophosphamide-treated mice, this influx of granulocytes into the peritoneal cavity was virtually eliminated, as was the concomitant increase in the number of blood granulocytes; in VP-16-treated mice, on the other hand, the number of peripheral blood and peritoneal granulocytes increased to the same degree as in normal mice. An increase in the number of peripheral blood monocytes and peritoneal macrophages occurred 24-48 h after injection of NBCS in normal mice. This increase was significantly impaired by irradiation as well as by treatment with cyclophosphamide or VP-16.

Acute hepatic injury after discontinuation of chemotherapy in a patient with non-Hodgkin's lymphoma and chronic hepatitis B virus infection.

We describe a HBsAg-positive patient with non-Hodgkin's lymphoma who underwent aggressive chemotherapy. After discontinuation of chemotherapy, he developed jaundice due to a reactivation of the hepatitis B. Serum HBeAg and HBV DNA turned positive, indicating active virus replication. Abdominal CT-scan showed a large solitary tumour mass in the liver and the serum alpha-fetoprotein level was extremely high, suggesting HBV-related hepatoma. After discontinuation of chemotherapy, the patient died of non-Hodgkin's lymphoma and hepatocellular carcinoma. Throughout treatment of HBsAg-positive patients with cytotoxic or immunosuppressive therapy, careful monitoring of serum aminotransferase levels and HBV DNA is essential. Aggressive chemotherapy may have to be discontinued or changed to a milder regimen if hepatitis occurs.

Uveitis during treatment of disseminated Mycobacterium avium-intracellulare complex infection with the combination of rifabutin, clarithromycin and ethambutol.

Three patients with a cellular immunodeficiency were treated with rifabutin, clarithromycin and ethambutol for a disseminated infection with Mycobacterium avium-intracellulare complex (MAC). The patients developed uveitis, sometimes in combination with a transient rash, arthralgia, arthritis, jaundice and pseudojaundice. It seems likely that these reactions were caused by rifabutin, alone or together with other drugs such as clarithromycin. These adverse reactions probably depend on the dose, metabolism and excretion of the drug. Inhibition of cytochrome P450 seems to be an important mechanism.

[Therapy of systemic mycoses in neutropenic patients using itraconazole. A comparative, randomized study with amphotericin B]. / Die Therapie von Systemmykosen neutropenischer Patienten mit Itraconazol. Eine vergleichende, randomisierte Studie mit Amphotericin B.

Systemic mycosis constitute a serious threat for the patient with granulocytopenia. The most important causative agents are Candida spp., Aspergillus spp. and, to a lesser extent, Cryptococcus neoformans, Mucoraceae and Pseudoallescheria boydii. Treatment of such infections with amphotericin B is difficult, because of the many side-effects of this medicine, such as hypotension, fever, shivering, thrombophlebitis, nephrotoxicity, renal tubular acidosis, hypokalaemia, anaemia and thrombocytopenia. In addition, the efficacy of amphotericin B in the treatment of proven mycotic infections in granulocytopenic patients is not very great. Itraconazole is a new, oral antifungal agent which is active in vitro and in animal experiments against both Candida and Aspergillus. In patients without granulocytopenia, itraconazole appeared to be effective in the treatment of deep Candida and Aspergillus infections. On the basis of the above data, a randomized comparative investigation was carried out unto the efficacy of amphotericin B and itraconazole in the treatment of systemic mycoses in neutropenic patients.