Modelled Target Attainment after Temocillin Treatment in Severe Pneumonia: Systemic and Epithelial Lining Fluid Pharmacokinetics of Continuous versus Intermittent Infusions.

The objective of this article is to describe the population pharmacokinetics (PK) of temocillin administered via continuous infusion (CI) versus intermittent infusion (II) in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Thirty-two mechanically ventilated patients who were treated for pneumonia with 6 g of temocillin daily for in vitro sensitive pathogens were assigned to either the II (2 g every 8 h over 0.5 h) or the CI (6 g over 24 h after a loading dose of 2 g) group. A population pharmacokinetic model was developed using unbound plasma, and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. The area under the concentration-time curve from 0 to 24 h (AUC0-24) ELF/plasma penetration ratio was 0.73, at steady state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed that for the minimal pharmacodynamic (PD) targets of 50% T > 1× MIC (II group) and 100% T > 1× MIC (CI group), PK/PD breakpoints were 4 mg/L in plasma and 2 mg/L in ELF and 4 mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with creatinine clearance (CLCR) < 60 mL/min/1.73 m2. While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in the case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia.

Continuous infusion of cefepime and neurotoxicity: a retrospective cohort study.

OBJECTIVES: Neurotoxicity related to cefepime is increasingly reported in the literature but specific data concerning continuous infusion (CI) of the drug are still lacking. Our primary objective was to evaluate the incidence of neurotoxicity related to CI of cefepime and the associated risk factors. Our secondary objectives were to analyse the plasma cefepime concentrations and to define the threshold above which neurotoxicity occurs. METHODS: In this single-centre retrospective cohort study, all adult patients who underwent at least one cefepime therapeutic drug monitoring (TDM) and were treated with CI of 4 g/day between January 2017 and June 2019 were included. Neurotoxicity was evaluated according to a strict definition and was correlated with steady-state concentration at the time of toxicity presentation. RESULTS: Ninety-eight patients with 201 cefepime TDM studies were included, with an incidence of neurotoxicity of 14.3% (14/98). Patients with neurotoxicity had more often underlying brain disease (35.7% (5/14) vs 11.9% (10/84), p = 0.030)) and higher steady-state concentrations (mean ± standard deviation 71.8 ± 32.9 mg/L vs 49.6 ± 30.6, p = 0.036) than the others. A receiver operating characteristic curve analysis yielded a cefepime steady-state concentration of 63.2 mg/L as the best cut-off point between patients with or without neurotoxicity. A mean steady-state concentration of 46.4 mg/L was achieved if the dosages of cefepime were adapted to renal function which was under our threshold concentration but above our highest pharmacokinetic/pharmacodynamic target of 32-40 mg/L. CONCLUSIONS: Our results suggest that 4 g/day of cefepime adapted to renal function and infused over 24 h is a trade-off for the risk/benefit ratio, when used empirically.

[Streptococcus agalactiae infective endocarditis]. / Endocardite infectieuse à Streptococcus agalactiae.

Infectious endocarditis is a rare pathology whose mortality is high and whose diagnosis is still difficult by the usual clinical, biological and ultrasound tools. We report the case of a patient, drug addict, suffering from an infectious endocarditis of the aortic valve at Streptococcus agalactiae. This germ is rarely at the origin of cardiac infection but it is responsible for quickly destructive lesion by its pathophysiological mechanisms. In this case, the infection unfortunately caused the death of the patient.

L'endocardite infectieuse est une pathologie rare dont la mortalité est élevée et dont le diagnostic reste encore difficile par les outils cliniques, biologiques et échographiques habituels. Nous rapportons le cas d'un patient, toxicomane, souffrant d'une endocardite infectieuse de la valve aortique à Streptococcus agalactiae. Ce germe est rarement à l'origine d'infection cardiaque, mais il est responsable de lésion rapidement destructrice par des mécanismes physiopathologiques qui lui sont propres. Dans ce cas particulier, cette infection a, malheureusement, occasionné le décès du patient.

[Emergency department utilization by HIV-positive adults in a Belgian setting]. / Etude des motifs d'admission au service des Urgences d'une cohorte de patients infectés par le VIH suivis au CHU de Liège.

The use of the emergency department (ED) by human immunodeficiency virus (HIV)-infected adults undergoes an evolution following the introduction of antiretroviral therapy (ART). Improving our knowledge about ED use characteristics will contribute to a correct diagnosis and therapeutic approach in this patient group, at the moment they are discharged from the ED. We conducted a one-year retrospective study on characteristics of ED use involving 1026 patients living with HIV. The majority of them was treated with antiretroviral therapy (95 %) and had a viral load lower than 50 copies (73.6 %). Among them, 117 patients (11.8 %) were admitted at least once to the ED. The most common ED discharge diagnoses were related to trauma (30 %). This study shows that the great majority of diagnoses were not related to infectious diseases (6.3 %, of which half were HIV-related). One hypothesis to explain these results would be that HIV-positive adults in this study had excellent antiretroviral coverage and were well controlled in terms of HIV.

L'utilisation du département des urgences (DU) par les adultes infectés par le virus de l'immunodéficience humaine (VIH) évolue suite à l'instauration des traitements antirétroviraux (TAR). Nous avons besoin d'améliorer nos connaissances à ce sujet et d'en savoir plus sur le diagnostic de ces patients lorsqu'ils quittent le service d'urgence. Nous avons réalisé une étude rétrospective sur une durée d'un an et qui s'intéresse aux caractéristiques de l'utilisation du DU par 1.026 patients vivant avec le VIH. La majorité d'entre eux était sous traitement anti-rétroviral (95 %) et avait une charge virale inférieure à 50 copies (73,6 %). Parmi eux, 117 (11,8 %) se sont présentés au moins une fois au DU. Les principaux motifs d'admission étaient d'ordre traumatologique (30 %). Cette étude montre que la grande majorité des motifs d'admission au DU des patients vivant avec le VIH n'était pas en rapport avec des pathologies infectieuses (seulement 6,3 %, dont la moitié directement liées au VIH). Une hypothèse pour expliquer ces résultats serait que les patients étudiés bénéficiaient d'une excellente couverture anti-rétrovirale et étaient bien contrôlés en termes de VIH.

[Infective endocarditis:an emergency well too minimized]. / Une urgence bien souvent méconnue.

Infective endocarditis is a rare disease that can lead to some diagnostic wandering because of its often nonspecific and polymorphic clinical manifestations. This latency is at the origin of severe cardiac and extra-cardiac complications, yet highly fatal. The clinician should always bear in mind the differential diagnosis of a patient with fever of undetermined origin, with risk factors for valve infection such as foreign material, and history recent invasive procedures (including dental procedures) or recent hospitalization. The current medical tools make it possible to highlight the infection and its complications in a fast and complete manner, so as not to delay the patient's management, particularly with the introduction of urgent empirical antibiotherapy.

L'endocardite infectieuse est une maladie rare pouvant entraîner une certaine errance diagnostique au vu de ses manifestations cliniques souvent aspécifiques et polymorphes. Cette latence est à l'origine de complications cardiaques et extra-cardiaques potentiellement mortelles. Le clinicien doit toujours avoir à l'esprit ce diagnostic différentiel face à un patient avec une fièvre d'origine indéterminée, et qui présente des facteurs de risque d'infection valvulaire tels qu'un matériel étranger, des antécédents récents de gestes invasifs (entre autres dentaires) ou d'hospitalisation récente. Les outils médicaux actuels permettent de mettre en évidence l'infection et ses complications de façon rapide et complète, afin de ne pas retarder la prise en charge du patient avec, notamment, l'instauration urgente d'une antibiothérapie empirique.

[Multidisciplinary management of a giant hepatic hydatidosis]. / Prise en charge multidisciplinaire d'une volumineuse hydatidose hépatique.

Cystic echinococcosis or hydatidosis, is a zoonosis caused by larval stages of Echinococcus granulosus that can be encountered in Belgium in patients originating from endemic countries. The liver is the most commonly affected organ. In this paper, the authors describe the multidisciplinary management of this pathology based on the clinical case of a patient suffering from a 28 cm cystic echinococcosis treated by combination of albendazole and liver resection. Several treatment options are described in the literature although there is currently no clear consensus on the management of this condition.

L'échinococcose cystique, appelée aussi hydatidose, est une zoonose causée par le développement chez l'homme de la larve d'un ténia échinocoque de type Echinococcus granulosus. Il s'agit d'une pathologie cosmopolite qui peut être rencontrée en Belgique chez des patients originaires de pays endémiques et qui atteint, le plus souvent, le foie. Dans cet article, les auteurs discutent la prise en charge multidisciplinaire de cette pathologie en partant du cas d'un patient souffrant d'un kyste échinococcique hépatique de 28 cm traité par albendazole et résection hépatique. Plusieurs options de traitement de l'échinococcose cystique sont décrites dans la littérature bien qu'il n'existe pas, à l'heure actuelle, de consensus clair concernant la prise en charge de cette pathologie.

[Endocarditis of mitral and aortic prosthetic heart valves caused by Aggregatibacter aphrophilus]. / Le cas clinique du mois. Endocardite à Aggregatibacter aphrophilus sur prothèses valvulaires.

We present the case of an acute endocarditis of mitral and aortic prosthetic heart valves caused by Aggregatibacter aphrophilus (Haemophilus aphrophilus-paraphrophilus). This third report in the literature emphasizes the diagnostic work-up and the role of positron emission tomography combined with computed tomography in this setting. The specificities of endocarditis due to the HACEK group (Haemophilus spp., Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella spp.) and the specific microbiological data and therapeutic options pertinent to this germ are discussed.

Nous rapportons la troisième observation clinique de la littérature d'une endocardite sur prothèses mécaniques mitrale et aortique due à l'Aggregatibacter aphrophilus (Haemophilus aphrophilus-paraphrophilus). Le pathogène récemment rebaptisé Aggregatibacter aphrophilus fait partie du groupe HACEK (Haemophilus spp., Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella spp.) impliqué dans des endocardites valvulaires de diagnostic difficile. Cette histoire clinique est l'occasion d'une revue de la littérature et des spécificités de ce pathogène. Elle met en exergue la contribution de la tomographie à émission de positons combinée à une tomodensitométrie dans le diagnostic et le suivi. Elle démontre, avec un recul de plus de deux ans, l'efficacité du traitement médical dans certaines endocardites sur prothèse.

[Management of chronic osteomyelitis by long-term antibiotic suppression]. / Prise en charge de l'ostéomyélite chronique par antibiothérapie suppressive au long cours.

Chronic osteomyelitis is a chronic inflammatory disease induced by bone infection. It may be limited to a single portion of bone or involve several areas such as marrow, cortical, periosteum and adjacent soft tissues. Being able to persist for weeks, months or even years, it remains a therapeutic challenge in spite of the important medical and surgical advances, with a prolonged and complex management given the nature of the surgical interventions and the antibiotherapies required. We report a case of chronic osteomyelitis treated by long-term suppressive antibiotic therapy, which may be a reasonable alternative to surgery in inoperable clinical situations, but taking into account the risks associated with it in terms of side effects and selection of resistant organisms, as well as the cost of treatment and the quality of life of the patient.

L'ostéomyélite chronique est une pathologie inflammatoire chronique induite par une infection osseuse. Elle peut être limitée à une seule portion d'os ou impliquer plusieurs zones telles que la moelle, la corticale, le périoste et les tissus mous adjacents. Pouvant persister pendant des semaines, des mois voire des années, elle reste un challenge thérapeutique en dépit des importantes avancées médicales et chirurgicales, avec une prise en charge prolongée et complexe compte tenu de la nature des interventions chirurgicales et des antibiothérapies requises. Nous rapportons un cas d'ostéomyélite chronique pris en charge par antibiothérapie suppressive au long cours, qui peut être une alternative raisonnable à la chirurgie dans des situations cliniques inopérables, mais en prenant en considération les risques qui y sont associés en termes d'effets secondaires et de sélection des germes résistants, ainsi que le coût du traitement et la qualité de vie du patient.

Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey.

This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 ± 10.4 % vs. 90.3 ± 6.6 %, p = 0.0013; antibiotics documented 87.9 ± 9.0 % vs. 95.6 ± 5.1 %, p < 0.0001; and duration or review date documented 31.9 ± 15.4 % vs. 67.7 ± 15.2 %, p < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.

[Hooping cough in adults, think about it!]. / Coqueluche chez l'adulte, pensez-y!

We report the case of a 47 year old patient who had been suffering from persistent cough for more than three weeks. Patient coughed predominantly during night time, without fever. The amoxicillin-clavulanic acid initially prescribed was not effective. A series of complementary investigations were performed before serology finally identified Bordetella pertussis infection after two months of symptoms which improved slowly without evident benefit of macrolide treatment. The diagnosis of whooping cough was also established for the wife of the patient with fast resolution of the symptoms after rapid unset of treatment with macrolides.

Drug-induced uveitis in aids patients: two case reports.

Patients with acquired immunodeficiency syndrome (AIDS) can develop severe uveitis. Although infectious and autoimmune causes must always be considered, drug induced uveitis is also an important etiology. Herein, we present two case reports illustrating the classical presentation of rifabutin and cidofovir induced uveitis. The first case was a 33 year old woman with AIDS treated with anti-protease and anti-tuberculosis drugs (including rifabutin). She presented with a red painful right eye. There was a strong anterior segment inflammation with fibrinous exudates and a dense vitritis. Rifabutin was stopped and topical steroids and mydriatics were given. Intraocular inflammation and symptoms rapidly resolved. The second patient was a 36 year old woman who presented with a painful decrease of vision in her left eye. She was followed for bilateral CMV retinitis in the setting of AIDS and had recently received 2 systemic injections of cidofovir. Anterior segment inflammation with posterior synechiae in both eyes and folds of Descemet membrane in the left eye were noted. Intraocular pressure was 0 mmHg in the left eye and 10 mmHg in the right eye. Fundus examination disclosed CMV retinitis scars in the right eye and choroidal folds in the macula of the left eye. Cidofovir was discontinued and topical steroids and mydriatics started. Progressively the inflammation decreased and the intraocular pressure returned to normal levels. In conclusion, rifabutin and cidofovir are classical examples of drug induced uveitis with distinct characteristic clinical presentation. Recognition of those entities in AIDS patients can avoid useless and potentially invasive interventions in those fragile people.

A pauci-symptomatic case of documented Hantavirus (Puumala) infection in a patient under anti-TNF treatment.

We describe the case of an 18-yr-old male under anti-TNF treatment for Crohn's disease for more than 8 months. He developed fever and biological inflammatory syndrome without absolutely no accompanying sign or symptom or paraclinical abnormality despite extensive work-up performed in the context of his immunocompromised state. Symptoms disappeared after 10 days and a diagnosis of Puumala infection was made retrospectively on a serological basis. The case illustrates that anti-TNF treatment does not worsen the course of Puumala infection and could even be associated with a milder clinical picture.

[Prophylaxis of infective endocarditis: improved dental care and oral health rather than systematic antibiotic prophylaxis?]. / Comment je préviens...l'endocardite infectieuse: une meilleure hygiène bucco-dentaire plutôt qu'une antibioprophylaxie systématique?

Prophylaxis for infective endocarditis has been recommended on the basis of the supposed pathophysiology of the disease, although no randomised clinical trial has confirmed its efficacy. Bacteraemia resulting from daily activities is much more likely to cause infective endocarditis than bacteraemia associated with invasive medical procedures. As a result, recommendations for antibiotic prophylaxis tend now to be severely restricted.

[Syphilis in 2008: practical aspects and controversies]. / Syphilis en 2008: controverses et attitudes pratiques.

Rising incidence rate of syphilis is observed in economically advanced countries, particularly among homosexual men and subpopulation with low socioeconomic status. The various clinical presentations are divided into early and late stages, including neurosyphilis. The latter can occur during any stage of the disease, leading to the question "when to perform lumbar puncture", particularly in HIV positive patients. Penicillin continues to be the first-line therapy for all stages of syphilis. An alternative treatment should be considered as an exemption, after advice from a specialist. All patients require prolonged clinical and serological follow-up after treatment to rule out relapse or re-infection. The diagnosis of syphilis is an opportunity to search and treat other sexually transmitted diseases in patients and their sexual partner(s).

Chronic hepatitis C infection in a patient with bone marrow hypoplasia.

Chronic hepatitis C virus (HCV) infection is associated with multifarious extra-hepatic manifestations; the most described and discussed being mixed cryoglobulinemia which is strongly related to B-cell lymphoproliferative disorders (LPDs). We present a case of chronic HCV infection and mixed cryoglobulinemia, with minimal liver involvement. The case is a 53-year-old patient who was diagnosed as having bone marrow hypoplasia at the age of three. She received several blood transfusions to normalize her haemoglobin. At the age of 31, she was diagnosed with rheumatoid arthritis on account of her diffuse joint pain and inflammation, elevated rheumatoid factor (RF) and Raynaud's phenomenon. Twenty years later, monoclonal gammopathy of IgG Lambda (one year later, changed to IgM Kappa) was detected during a routine examination. A bone marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade malignant lymphoma cells. PCR of the bone marrow aspirate was not contributory. No treatment was initiated owing to her poor bone marrow function and she is under regular follow-up.

[New treatments of infectious diseases over the last ten years]. / Avancées thérapeutiques en pathologie infectieuse au cours de la dernière décennie.

This review focuses on new antibiotics, particularly for gram-positive infections, new antiretroviral drugs, new treatment of fungal infections and indications of miltefosine in the treatment of leishmaniasis.