Frédéric Frippiat

Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients.

Objectives: To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients. Design: Single-center, prospective, randomized controlled study. Setting: Five intensive care units from a tertiary teaching hospital. Patients: All consecutive adult patients hospitalized for > 48 hrs in the intensive care unit during a 9-month period. Interventions: Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist. Measurements and Main Results: There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6 ± 34.4% and 57.7 ± 34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p = .11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value >1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels <0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve = 0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician. Conclusions: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.

Prevention of ventilator-associated pneumonia and ventilator-associated conditions: A randomized controlled trial with subglottic secretion suctioning

Objectives:Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use. Design:Randomized controlled clinical trial conducted in five ICUs of the same hospital. Patients:Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2). Main Results:During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory days, ventilator-associated pneumonia rates were 9.6 of 1,000 ventilatory days and 19.8 of 1,000 ventilatory days, respectively (p = 0.0076). Ventilator-associated condition prevalence was 21.8% in group 1 and 22.5% in group 2 (p = 0.84). Among the 47 patients with ventilator-associated pneumonia, 25 (58.2%) experienced a ventilator-associated condition. Neither length of ICU stay nor mortality differed between groups; only ventilator-associated condition was associated with increased mortality. The total number of antibiotic days was 1,696 in group 1, representing 61.6% of the 2,754 ICU days, and 1,965 in group 2, representing 68.5% of the 2,868 ICU days (p < 0.0001). Conclusions:Subglottic secretion suctioning resulted in a significant reduction of ventilator-associated pneumonia prevalence associated with a significant decrease in antibiotic use. By contrast, ventilator-associated condition occurrence did not differ between groups and appeared more related to other medical features than ventilator-associated pneumonia.

Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study

OBJECTIVES The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. PATIENTS AND METHODS Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method. RESULTS Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma. CONCLUSIONS The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.

Downregulation of CD94/NKG2A inhibitory receptors on CD8+T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells.

Fatal Alveolar Echinococcosis of the Lumbar Spine

ABSTRACT For the last 10 years, the southern part of Belgium has been recognized as a low-risk area of endemicity for alveolar echinococcosis. This infection, caused by Echinococcus multilocularis, usually induces a severe liver condition and can sometimes spread to other organs. However, alveolar echinococcosis involving bones has been described only very rarely. Here, a fatal case of spondylodiscitis due to E. multilocularis contracted in southern Belgium is reported.

Report of a Case of Streptococcus agalactiae Mycotic Aneurysm and Review of the Literature

A unique case of mycotic aneurysm of the abdominal aorta caused by Streptococcus agalactiae in an afebrile patient presenting with abdominal pain is described. Although this bacterium is associated with a variety of infections in human beings, aortitis is uncommon. Chronic alcoholism and diabetes mellitus are the 2 major predisposing conditions for group B Streptococci infection and both were present in this case. The abdominal pain and elevated inflammatory markers in the absence of fever were elusive in presentation; however, the diagnosis of mycotic aneurysm was established by abdominal computed tomography scan. The patient was treated successfully by resection of the diseased aorta and aortic allograft replacement. Culture of the excised tissue grew Streptococcus agalactiae sensitive to penicillin G and (other commonly tested antibiotics) fluoroquinolones. A prolonged course of moxifloxacin (for 6 months) was administered due to the persistence of elevated inflammatory markers and was remarkably well tolerated. Sixteen months after stopping the antibiotics, the patient is doing well, and the control imaging studies are satisfactory.

Decline of antibiotic use in primary care

We agree with Jarold Cosby and colleagues that the largest volumes of antibacterial agents are prescribed in primary care, with respiratory tract infections being the most common indication. However, we are surprised by the authors statement that “the amount of antibiotics prescribed in primary care declined during 1995–2005 in most more developed countries, including Sweden, England and Wales, and the USA”. The European Surveillance of Antimicrobial Consumption project published data on outpatient antibiotic use in 25 European countries during 1997– 2003. Several temporal patterns were observed: continuous increase in Greece, Croatia, Ireland, Portugal, Luxembourg, and Denmark; an initial increase followed by a decrease in France, Czech Republic, Hungary, Poland, Slovenia, and Sweden; and an initial decrease followed by an increase in the UK, Belgium, and Spain. Globally, the volume of outpatient antibiotic use expressed in defi ned daily dose per 1000 inhabitants per day (DDD) has increased in most European countries between 1997 and 2003. Moreover, increased use of broad-spectrum antibiotics such as amoxicillin/ clavulanic acid, macrolides, and quinolones, and higher prescription rates during winter months were noted with an obvious exception in several northern European countries. Since most respiratory tract infections are of viral origin and self-limiting, excessive consumption of antibiotics in winter suggests their inappropriate use in this setting. In Belgium, notwithstanding the national campaign to improve antibiotic use initiated in 2000, the problem is particularly notable. This is illustrated by the increase in DDD of fl uoroquinolones from 1·69 in 1993 to 2·98 in 2003, thereby placing Belgium in third position as the largest consumer of this class of antibiotics in Europe. A retrospective study by the Belgian National Institute of Health in March, 2006, indicated that 85% of 111 821 outpatient fl uoroquinolone prescriptions were made by family doctors. Furthermore, 32·4% of these 10 940 physicians prescribed at least ten diff erent courses of fl uoroquinolone in 1 month, which represents 68·5% of the total prescriptions. 210 of these “superprescribers” were interviewed about the fi nal diagnosis of their 2556 prescriptions (based on the patient fi les). Nine groups of pathologies were identifi ed and appropriateness of fl uoroquinolone was considered as per the guidelines published by the National Institute of Health and the Belgian Antibiotics Policy Coordination Committee. Inappropriate prescriptions were observed in 77·4% of 2102 prescriptions for which a diagnosis was established, including acute bronchitis (28·6%) uncomplicated urinary tract infection (26·4%), and upper respiratory tract infection (15·3%). Additionally, of the 75 (22·6%) “correct” use prescriptions, 4·4% were indicated for community-acquired pneumonia and 9·3% were prescribed for abdominal infections (mainly acute gastroenteritis)—for which fl uoroquinolones are not the fi rst-line therapy. Hence, inappropriate use occurs more than 77·4% of the time. Moxifl oxacin accounts for the most of these inappropriate prescriptions (36% out of 2556) and was prescribed regularly for acute bronchitis (79·5%) and upper respiratory tract infections (77%). We believe a gap persists between recommended good clinical practice on ambulatory antimicrobial therapy and “real life” practice; therefore, decline in antibiotic use is not the rule in most European countries.

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 Crohns 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.

Autoimmune Angioneurotic Edema in a Patient with Helicobacter pylori Infection

Association of acquired autoimmune angioneurotic edema with other diseases is increasing. However, the precise mechanism by which antibodies to C1‐esterase inhibitor (C1‐INH) are produced, is not elucidated. We describe a patient with IgA antibodies against C1‐INH without other autoimmune markers. Our patient had gastritis and Helicobacter pylori infection, proven by biopsy. This case suggests that H. pylori infection can act as triggering factor for acquired autoimmune angioneurotic edema.

Factors associated with late presentation for HIV care in a single Belgian reference center: 2006–2017

Late presentation for HIV care is a major issue and the cause of higher morbidity, mortality and transmission. In this regard, we analyzed the characteristics of patients presenting for care at our center from January 2006 to July 2017 (n = 687). The majority of the studied population was of African origin (54.3%) with heterosexual women representing the main group (n = 292; 42.5%). 44% of the patients were late presenters (LP) (presenting for care with CD4 T cells <350/mm3 or an AIDS defining event) and 24% were late presenters with advanced disease (LP-AD) (presenting for care with CD4 T cells <200/mm3 or an AIDS defining event). A very high risk of being LP and LP-AD was associated with Sub-Saharan origin (OR 3.4 and 2.6 respectively). Other factors independently associated with LP or LP-AD were age (OR 1.3), male gender (OR 2.0 and 1.5 respectively) and heterosexual route of transmission (OR 2.4 and 2.3 respectively). A significant increase in HIV screening without forgetting those groups would contribute to earlier HIV diagnosis, a key element to end the HIV epidemic. To achieve this goal, addressing the specific hurdles to HIV testing in the migrant population is critical.