Rifampin levels in daily practice: the accuracy of a single measurement.

BACKGROUND: Measurement of rifampin levels is not part of routine practice. However, low levels are associated with failure of tuberculosis treatment. The clinical relevance of serum levels in daily practice is unclear. The objective was to evaluate rifampin serum concentrations and factors associated with insufficient concentrations. METHODS: Patients with at least one rifampin concentration drawn 3 hours after intake (C3) between 2005 and 2014 were included. Data on demographic and clinical characteristics were collected, including side effects and dose adjustments. Two different criteria were used to define adequate concentrations (criterion 1: C3 a nd C 6 ≥ 3 mg/l; criterion 2: C3 or C6 ≥ 5 mg/l). RESULTS: Of 63 patients, 66% and 76% had a sufficient level according to criterion 1 or 2, respectively. C3 exceeded C6 in most patients, while a late maximum was significantly associated with diabetes mellitus (p = 0.003). A dose adjustment was made in 19% of cases, more frequently in patients with insufficient levels (p = 0.02) or with ≥ 2 side effects (p = 0.03). CONCLUSION: Rifampin levels varied but were mostly adequate and a single measurement at 3 hours after intake provided the required information in most cases, indicating that full AUC0-24 measurements could be limited to specific situations.

Diagnostic imaging of hepatic tuberculosis: case series.

BACKGROUND: Hepatic tuberculosis (TB) shows non-specific symptoms, and liver imaging may provide diagnostic clues. Here we describe a series of patients with hepatic TB showing characteristic radiological findings. METHODS: Single-centre retrospective evaluation of patients with hepatic TB diagnosed over a period of 16 years who underwent ultrasound, computed tomography (CT) and/or magnetic resonance imaging (MRI). Hepatic lesions were classified as miliary, nodular, serohepatic or cholangitis. RESULTS: Of 14 patients with hepatic TB, five were co-infected with the human immunodeficiency virus. All patients had additional extrahepatic TB localisations. An interferon-gamma release assay was performed in 11/14 patients, ultrasound and CT were available for all patients and MRI for four. Observed patterns were miliary (n = 6) with multiple nodules < 2 cm; nodular (n = 5), characterised by a variable number of nodules (2-7 cm); and serohepatic (n = 3), with multiple nodular subcapsular lesions with a thin, smooth wall. Shared findings were hypoechoic lesions on ultrasound, hypodense lesions with ring enhancement on CT, while MRI lesions were hypointense on T1- and hyperintense on T2-weighted images. CONCLUSIONS: Ultrasound, CT and MRI can independently contribute to detection of hepatic TB. While a miliary pattern or calcifications are characteristic, no pattern is completely pathognomonic and the diagnosis depends on microbiological evidence. Particularly in risk groups, characteristic radiological findings may prompt targeted diagnostic work-up.

Donor-derived tuberculosis via orthotopic liver transplantation.

We present a case of donor-derived tuberculosis after liver transplantation, in which the donor origin of the Mycobacterium tuberculosis isolate was made most likely by DNA fingerprinting. Screening for latent tuberculosis of transplant donors originating from high endemic areas with an ex-vivo interferon-gamma release assay should be considered.

A critical assessment of the association between postnatal toxoplasmosis and epilepsy in immune-competent patients.

While postnatal toxoplasmosis in immune-competent patients is generally considered a self-limiting and mild illness, it has been associated with a variety of more severe clinical manifestations. The causal relation with some manifestations, e.g. myocarditis, has been microbiologically proven, but this is not unequivocally so for other reported associations, such as with epilepsy. We aimed to systematically assess causality between postnatal toxoplasmosis and epilepsy in immune-competent patients. A literature search was performed. The Bradford Hill criteria for causality were used to score selected articles for each component of causality. Using an arbitrary but defined scoring system, the maximal score was 15 points (13 for case reports). Of 704 articles, five case reports or series and five case-control studies were selected. The strongest evidence for a causal relation was provided by two case reports and one case-control study, with a maximal causality score of, respectively, 9/13, 10/13 and 10/15. The remaining studies had a median causality score of 7 (range 5-9). No selection bias was identified, but 6/10 studies contained potential confounders (it was unsure whether the infection was pre- or postnatal acquired, or immunodeficiency was not specifically excluded). Based on the evaluation of the available literature, although scanty and of limited quality, a causal relationship between postnatal toxoplasmosis and epilepsy seems possible. More definite proof requires further research, e.g. by performing Toxoplasma serology in all de novo epilepsy cases.

[Associated injuries with greater tuberosity fractures : Mechanism of injury, diagnostics, treatment]. / Begleitverletzungen bei Tuberculum-majus-Frakturen : Entstehungsmechanismus, Diagnostik, Therapie.

BACKGROUND: To date, little attention has been given to greater tuberosity fractures (GTFs) in the literature. Several mechanisms of injury are described, but few authors report that a GTF is accompanied by a high rate of often unrecognized associated injuries. OBJECTIVES: The aim was to document the incidence of dislocation, to diagnose associated injuries and, based on these, these draw conclusions about the mechanism of injury concerning GTF. PATIENTS AND METHODS: From 2007-2015 the detection of a shoulder dislocation, the fracture extent (displacement, fragments, size), associated injuries, and the surgical treatment of GTF and associated injuries were documented in 46 patients with GTF who were less than 65 years of age. After detection of associated injuries by computed tomography, magnetic resonance imaging (MRI) or arthroscopy it was decided if surgery was necessary or not. RESULTS: Shoulder dislocation was found in 46.2 % of patients with a 1-fragmentary GTF. Shoulder dislocation was found in 66.7 % of patients with a 2-fragmentary GTF and 100 % of patients with ≥3 fragments.. Typical injuries associated with dislocation were found in 90.7 %. In 52.6 % of these surgery was necessary. With or without dislocation, approximately the same prevalence of associated injuries was present (92.6 %; 87.5 %). With dislocation surgery for the associated injuries was necessary in 70.8 %; without dislocation surgery was necessary in 35.7 %. DISCUSSION: The reason for a GTF seems to be an anterior shoulder dislocation or partial dislocation. In multifragmentary GTF or GTF with dislocation surgery is necessary frequently; without dislocation surgery is necessary less frequently. Associated injuries should be searched for selectively. An arthroscopy could be performed for diagnosis and therapy. In a GTF that can be treated conservatively, an MRI should be performed.

Impact of balanced tetrastarch raw material on perioperative blood loss: a randomized double blind controlled trial.

BACKGROUND: As 6% hydroxyethyl starch (HES) 130/0.40 or 130/0.42 can originate from different vegetable sources, they might have different clinical effects. The purpose of this prospective, randomized, double-blind controlled trial was to compare two balanced tetrastarch solutions, one maize-derived and one potato-derived, on perioperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We randomly assigned 118 patients undergoing elective cardiac surgery into two groups, to receive either a maize- or a potato-derived HES solution. Study fluids were administered perioperatively (including priming of CPB) until the second postoperative day (POD#2) using a goal directed algorithm. The primary outcome was calculated postoperative blood loss up to POD#2. Secondary outcomes included short-term incidence of acute kidney injury (AKI), and long-term effect (up to one yr) on renal function. RESULTS: Preoperative and intraoperative characteristics of the subjects were similar between groups. Similar volumes of HES were administered (1950 ml [1250-2325] for maize-HES and 2000 ml [1500-2700] for potato-HES; P=0.204). Calculated blood loss (504 ml [413-672] for maize-HES vs 530 ml [468-705] for potato-HES; P=0.107) and the need for blood components were not different between groups. The incidence of AKI was similar in both groups (P=0.111). Plasma creatinine concentration and glomerular filtration rates did vary over time, although changes were minimal. CONCLUSIONS: Under our study conditions, HES 130/0.4 or 130/0.42 raw material did not have a significant influence on perioperative blood loss. Moreover, we did not find any effect of tetrastarch raw material composition on short and long-term renal function. CLINICAL TRIAL REGISTRATION: EudraCT number: 2011-005920-16.

General practitioner reported incidence of Lyme carditis in the Netherlands.

BACKGROUND: Between 1994 and 2009, incidence rates of general practitioner (GP) consultations for tick bites and erythema migrans, the most common early manifestation of Lyme borreliosis, have increased substantially in the Netherlands. The current article aims to estimate and validate the incidence of GP-reported Lyme carditis in the Netherlands. METHODS: We sent a questionnaire to all GPs in the Netherlands on clinical diagnoses of Lyme borreliosis in 2009 and 2010. To validate and adjust the obtained incidence rate, medical records of cases of Lyme carditis reported by GPs in this incidence survey were reviewed and categorised according to likelihood of the diagnosis of Lyme carditis. RESULTS: Lyme carditis occurred in 0.2 % of all patients with GP-reported Lyme borreliosis. The adjusted annual incidence was six GP-reported cases of Lyme carditis per 10 million inhabitants, i.e. approximately ten cases per year in 2009 and 2010. CONCLUSIONS: We report the first incidence estimate for Lyme carditis in the Netherlands, validated by a systematic review of the medical records. Although Lyme carditis is an uncommon manifestation of Lyme borreliosis, physicians need to be aware of this diagnosis, in particular in countries where the incidence of Lyme borreliosis has increased during the past decades.

Endovascular Aneurysm Repair (EVAR) : A Ten-Year Retrospective Study in a Low-Volume Center.

BACKGROUND: We evaluated clinical outcomes of EVAR procedures at a low-volume center in Belgium. We also analyzed the time before endoleak appeared. METHODS: We reviewed 77 EVAR procedures performed over 10 years in a low-volume center. Patients were reviewed at intervals of 1, 3, 6, 12, 24 and 36 months. RESULTS: The deployment of the endograft was successful for 76 of the 77 patients (98.7%). Perioperative mortality was 1.3%. Cardiac infarctus was reported in 5.19% of patients, 1.3% suffered hematoma, 1.3% renal insufficiency, 7.8%-respiratory diseases, and 2.6% strokes. The mortality rate during the first postoperative year was 9% and none of these deaths were AAA related. One endograft thrombosis was reported (1.3%) and there were no cases of endograft migration. Type 1 endoleak occurred in 3.9% of patients, and Type 2 in 22.1%. No other type of endoleak was reported. The mean period before endoleak diagnosis was 9.8 months. Two patients needed to be re-operated for a Type 1 endoleak. CONCLUSION: Performing EVAR procedures in a low-volume center did not increase morbidity and mortality risks. This is probably because the primary factor is the volume of procedures carried out by the surgeon, rather than the institution. EVAR follow-up is needed to diagnose endoleak, which can appear several months after.

Grading of a positive sputum smear and the risk of Mycobacterium tuberculosis transmission.

SETTING: After the diagnosis of a case of tuberculosis (TB), contact tracing is directed by the risk of transmission, for which sputum acid-fast bacilli (AFB) staining results are highly relevant. Limited data are available on the effect of the degree of acid-fast positivity, of a polymerase chain reaction (PCR) result or of bronchoalveolar lavage (BAL) fluid results on the risk of transmission. OBJECTIVES: To investigate factors associated with TB transmission, focusing on quantitative sputum smear results. DESIGN: Retrospective study of contact investigations performed over a period of 5 years in a Dutch Municipal Health Service among all index patients with TB, and the tuberculin skin test and chest radiography results in contacts. Three definitions of transmission were used: ≥ 1 or ≥ 5 contacts with positive TST or active TB in contacts. RESULTS: The highest (+4/+5) sputum AFB grades were associated with the highest relative risk (≥ 8) of extensive transmission or active TB among contacts. Novel risk factors observed were employment or school attendance, positive PCR of sputum and positive AFB staining of BAL fluid. Pulmonary symptoms, infiltrate or cavity and positive AFB sputum stain were also associated with transmission, confirming previous studies. CONCLUSION: The risk factors observed in this study may aid in the extension of contact investigations.

Predictive value for progression to tuberculosis by IGRA and TST in immigrant contacts.

The authors determined the positive predictive value (PPV) for progression to tuberculosis (TB) of two interferon-gamma release assays (IGRAs), QuantiFERON-TB Gold In-tube (QFT-GIT) and T-SPOT.TB, and the tuberculin skin test (TST) in immigrants contacts. Immigrant close contacts of sputum smear-positive TB patients were included when aged > or =16 yrs and their TST result was > or =5 mm 0 or 3 months after diagnosis of the index patient. Contacts were followed for the next 2 yrs for development of TB disease. Of 339 immigrant contacts with TST > or =5 mm, 324 and 299 had valid results of QFT-GIT and T-SPOT.TB, respectively. Nine contacts developed active TB. One patient had not been tested with TST, while another patient had not been tested with QFT-GIT and T-SPOT.TB. The PPV for progression to TB during this period was 9/288 = 3.1% (95% CI 1.3-5.0%) for TST > or =10 mm, 7/184 = 3.8% (95% CI 1.7-5.9%) for TST > or =15 mm, 5/178 = 2.8% (95% CI 1.0-4.6%) for QFT-GIT and 6/181 = 3.3% (95% CI 1.3-5.3%) for T-SPOT.TB. Sensitivity was 100%, 88%, 63% and 75%, respectively. The predictive values of QFT-GIT, T-SPOT.TB and TST for progression to TB disease among immigrant close contacts were comparable.

Interferon-gamma release assays in immigrant contacts and effect of remote exposure to Mycobacterium tuberculosis.

OBJECTIVE: To assess the association between remote exposure to tuberculosis (TB) and results of the tuberculin skin test (TST), and two interferon-gamma release assays (IGRAs)-QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB-in immigrant contacts of sputum smear-positive TB patients. METHODS: Immigrants aged >or=16 years in close contact with smear-positive TB patients were included. QFT-GIT and T-SPOT.TB were performed if the TST induration size was >or=5 mm. Associations between test results and origin from an endemic country were assessed. RESULTS: Of 433 close contacts, 322 (74%) had TST >or=5 mm, of whom, 282 (88%) had valid test results for all assays. Positive QFT-GIT results were obtained for 152/282 (54%) and positive T-SPOT.TB for 168/282 (60%). After adjustment for age, sex and recent contact, positive IGRA results and TST results >/=10 mm were found to be more frequent among immigrants who originated from Africa, in particular sub-Saharan Africa. CONCLUSION: When IGRAs are used to determine latent TB infection in foreign-born individuals, positive findings not only relate to recent TB infection, but also reflect prior TB exposure in the country of origin. This late reactivity will limit their usefulness in contact investigations among immigrants originating from endemic areas.

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement.

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

Interferon-gamma release assays during follow-up of tuberculin skin test-positive contacts.

SETTING: Following a large-scale contact investigation, individuals with a positive tuberculin skin test (TST) result were offered preventive tuberculosis treatment. OBJECTIVE: To investigate the effect of isoniazid (INH) treatment and the effect of time on interferon gamma release assay (IGRA) results during follow-up. DESIGN: TST-positive subjects (n = 122) detected during the large-scale contact investigation were included in the study. Blood was obtained every 6 months over 2 years to perform both tests. RESULTS: Preventive INH treatment was completed by 36 of the 122 (29.5%) subjects, 71 (58.2%) were followed up with 6-monthly X-ray screening and 15 (12.3%) did not complete INH treatment. The overall percentage of individuals with a positive result remained stable during the 2 years, at approximately 45-50%, but individual responses varied over time. The majority of initially low IGRA results remained below the cut-off value, initially high IGRA results remained positive, while initially intermediate IGRA results were followed by more dynamic patterns. CONCLUSION: This study showed a highly variable pattern of IGRA responses over time and suggests limited value for their use during follow-up of latently infected individuals. However, the significance of different kinetic patterns observed among subjects with intermediate initial IGRA results warrants further study.

Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific interferon-gamma assay.

Recently, interferon-gamma release assays (IGRA) for specific diagnosis of Mycobacterium tuberculosis infection have become available. In recent UK tuberculosis (TB) guidelines, it has been advised to screen for latent M. tuberculosis infection using the tuberculin skin test (TST), followed by IGRA if the TST is positive. Since TST can boost immune responses to tuberculin, the present authors evaluated whether TST administration affects the result of QuantiFERON-TB Gold in-tube (QFT-GIT), a whole blood-based IGRA. QFT-GIT was performed on the day of TST administration and the day of reading in 15 TST-negative subjects, 46 TST-positive subjects with recent or remote exposure to M. tuberculosis and five cured TB patients. No systematic boosting of QFT-GIT responses from negative to positive was observed. Only in a few TST-positive persons did TST enhance pre-existing QFT-GIT responses. Screening for latent Mycobacterium tuberculosis infection using tuberculin skin testing followed by interferon-gamma release assays on the day of reading is a reliable approach, as the specificity of QuantiFERON-TB Gold in-tube is not affected by prior tuberculin skin test administration.

Risk factors of acute hepatic failure during antituberculosis treatment: two cases and literature review.

Hepatotoxicity is a well-known side effect of antituberculosis treatment (ATT). If not recognised in time, drug-induced hepatitis can develop, which may rapidly progress to acute liver failure. We describe two patients with acute hepatic failure caused by ATT, whose pretreatment liver function had been normal. Both patients successfully underwent liver transplantation. Possible risk factors predisposing towards ATT-induced hepatic failure were evaluated, and at least four risk factors were present in these patients. Although available guidelines do not advocate routine monitoring of liver function during ATT unless baseline values are elevated or in the case of pre-existent liver disease, this is nevertheless common practice. Liver function should always be measured in patients who develop symptoms during ATT, and rising liver function parameters should prompt immediate action to prevent the occurrence of liver failure. This report underscores that regular monitoring of liver function parameters and adherence to guidelines is especially important in patients with risk factors for ATT-induced liver disease. An evaluation of chronic viral hepatitis in risk groups before starting ATT could be worthwhile.

Prospective controlled study of the diagnostic value of skin biopsy in patients with presumed meningococcal disease.

Microbiological tests for diagnosis of acute meningococcal disease are important for the clinical management of patients with this often-fatal illness, but cultures are frequently negative after antibiotics have been administered. Retrospective studies suggest that examination of skin biopsies may aid a rapid diagnosis and that cultures of skin biopsies are often positive even after antimicrobial treatment has commenced. This prospective controlled study aimed to assess the diagnostic value of skin biopsy compared with investigations of blood and cerebrospinal fluid (CSF) in patients with skin lesions and presumed meningococcal disease. A total of 43 patients, 31 with suspected acute meningococcal infection and 12 controls, were included. All skin biopsies were investigated by Gram stain and routine microbiological culture. In 25 patients, meningococcal infection was diagnosed microbiologically. The clinical diagnosis was meningococcal meningitis in 8 patients, meningococcal sepsis in 11 patients, and a combination of both in 6 patients. The sensitivity of cultures of blood, CSF, and skin biopsies was 56%, 50%, and 36%, respectively. When culture and Gram stain were combined, positive results were obtained in 56%, 64%, and 56%, respectively. There was no correlation between the diagnostic yield of skin biopsies and previous antibiotic treatment. In 14 patients, the diagnosis was based exclusively on one positive sample: CSF in 7 (28%) patients, blood in 4 (16%) patients, and skin biopsy in 3 (12%) patients. The sensitivity of skin biopsies was highest in patients with the least extensive skin lesions. Specificity was 100%. Microbiological investigation of skin biopsies increased the diagnostic yield and could be considered a component of the routine diagnostic work-up in patients with suspected meningococcal infection, even after the initiation of antimicrobial treatment.

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.