Exposure to intravenous posaconazole in critically ill patients with influenza: A pharmacokinetic analysis of the POSA-FLU study.

BACKGROUND: Data on posaconazole in the critically ill are scarce. In the POSA-FLU study, we examined the prevention of influenza-associated pulmonary aspergillosis with posaconazole in this population. METHODS: In this observational sub-study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24 h-dosing interval on both an early (Day 2 or 3) and a later (≥Day 4) treatment day. RESULTS: Target attainment was shown for AUC0-24 and Cmin prophylaxis but not for Cmin treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. CONCLUSIONS: Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population.

Successful Outcome of Disseminated Fusarium musae Fungemia with Skin Localization Treated with Liposomal Amphotericin B and Voriconazole in a Patient with Acute Myeloid Leukemia.

Fusarium spp. may cause invasive disseminated infections in immunocompromised patients, associated with significant morbidity and mortality. We describe a case of disseminated fusariosis with fungemia and skin localization caused by Fusarium musae in a patient with acute myeloid leukemia successfully treated using liposomal amphotericin B and voriconazole.

A case of a surgical-site infection with Staphylococcus condimenti.

INTRODUCTION: Coagulase-negative staphylococci (CNS) are considered to have a medium or low pathogenic capacity when compared to S. aureus. Among the more harmless, CNS are those that are used in the food industry, represented by S. carnosus, whose genome has extensively been studied. Its genome was found to contain several genomic sequences that have a virulent function in the pathogenic S. aureus. Even though these genes are probably not virulent in S. carnosus, their presence might indicate a more virulent potential. We report the third clinical case associated with a surgical-site infection with S. condimenti, which belongs to these food industry related CNS. It corresponds to a blood stream infection, secondary to a surgical-site infection. RESULTS: Antibiotic susceptibility testing indicated a resistance to erythromycin and rifampicin, which was partly confirmed by the presence of a macrolide resistance gene by PCR screening for S. aureus virulence factors. Although no other putative virulence factors were detected, this organism managed to cause a severe post-operative wound infection. CONCLUSION: This case shows that CNS that are currently used in the food industry may play a role in human infection. With technologies such as MALDI-TOF, pathogens that are regarded non-pathogenic could be identified more often. Therefore, the risk of different Staphylococcus strains used in the food industry must be better assessed.

A disseminated Mycoplasma hominis infection in a patient with an underlying defect in humoral immunity.

Non-urogenital Mycoplasma hominis infections are rare, but may cause life-threatening complications. We describe a case of disseminated M. hominis infection with extensive abscess formation in an immunocompromised patient with iatrogenic hypogammaglobulinemia under rituximab treatment.

Nationwide Surveillance of Azole Resistance in Aspergillus Diseases.

Aspergillus disease affects a broad patient population, from patients with asthma to immunocompromised patients. Azole resistance has been increasingly reported in both clinical and environmental Aspergillus strains. The prevalence and clinical impact of azole resistance in different patient populations are currently unclear. This 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on Aspergillus resistance among patients with Aspergillus disease in Belgium. Isolates were prospectively collected in 18 hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and treatment data were collected with a questionnaire. The outcome was evaluated to 1 year after a patient's inclusion. A total of 220 Aspergillus isolates from 182 patients were included. The underlying conditions included invasive aspergillosis (n = 122 patients), allergic bronchopulmonary aspergillosis (APBA) (n = 39 patients), chronic pulmonary aspergillosis (n = 10 patients), Aspergillus bronchitis (n = 7 patients), and aspergilloma (n = 5 patients). The overall azole resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis, aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive aspergillosis was 52.5%, while susceptibility testing revealed azole resistance in only 2/58 of the deceased patients. The clinical impact of Aspergillus fumigatus resistance was limited in our patient population with Aspergillus diseases.

Infections caused by hypervirulent Klebsiella pneumoniae in non-endemic countries: three case reports and review of the literature.

OBJECTIVES: Spontaneous liver abscess caused by a hypervirulent Klebsiella pneumoniae strain was first described several decades ago in Taiwan and has been an emerging clinical entity worldwide ever since. We aimed to describe the clinical and microbiological characteristics of this infection in a non-endemic setting. METHODS: A narrative literature review was conducted in PubMed for European case reports of hypervirulent Klebsiella pneumoniae from 2016 to 2021. RESULTS: Forty case reports were retrieved. Mean age of the patients was 59 years and 72% were male. Diabetes mellitus was present in 33%. Twenty percent of the patients originated from an endemic region. A liver abscess and bacteremia were observed in, respectively, 83% and 80% of the cases. The most frequent metastatic infections were found in the eye (28%) and the lungs (28%). The sensitivity of molecular capsular antigen detection and the string test was 87% and 92%, respectively. Sixty-three percent of the strains had a wildtype resistance. CONCLUSION: Hypervirulent Klebsiella pneumoniae infections in non-endemic countries are most frequently observed in middle-aged males. Clinicians should be vigilant for metastatic infections.

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. METHODS: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit's binding sites over time. RESULTS: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2-4.7) mg/L under ECMO and 2.5 (1.4-3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. CONCLUSIONS: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

Cross-border dissemination of methicillin-resistant Staphylococcus aureus, Euregio Meuse-Rhin region.

Because the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) differs among the 3 countries forming the Euregio Meuse-Rhin (EMR) region (Belgium, Germany, and the Netherlands), cross-border healthcare requires information about the spread of MRSA in the EMR. We investigated the emergence, dissemination, and diversity of MRSA clones in the EMR by using several typing methods. MRSA associated with clonal complexes 5, 8, 30, and 45 was disseminated throughout the EMR. Dutch isolates, mainly associated with sequence types (ST) ST5-MRSA-II, ST5-MRSA-IV, ST8-MRSA-IV, and ST45-MSRA-IV had a more diverse genetic background than the isolates from Belgium and Germany, associated with ST45-MRSA-IV and ST5-MRSA-II, respectively. MRSA associated with pigs (ST398-MRSA-IV/V) was found in the Dutch area of the EMR. Five percent of the MRSA isolates harbored Panton-Valentine leukocidin and were classified as community-associated MRSA associated with ST1, 8, 30, 80, and 89.

Imported malaria and artemisinin-based combination therapy failure in travellers returning to Belgium: A retrospective study.

BACKGROUND: Malaria (Plasmodium spp) remains a top cause of travel-associated morbidity among European residents. Here, we describe recent trends of imported malaria to Belgium and characterize the first cases of P.falciparum failure to artemisinin-based combination therapy (ACT). METHODS: National surveillance data and registers from national reference laboratory were used to investigate malaria cases and ACT failures in the past 20 years. Recurrent infections were confirmed by pfmsp genotyping and polymorphisms in drug resistance-associated genes pfk13, pfcrt, pfmdr1, pfpm2, pfap2mu and pfubp1 were determined by sequencing or quantitative PCR. RESULTS: Annual malaria cases steadily increased in the last decade, reaching 428 in 2017 (all species). An estimated 15% of P.falciparum cases were severe. Between 2014 and 2017, 727 P.falciparum cases were reported and six non-immune travellers presented late recurrence. Five had hyperparasitaemia and/or signs of severe malaria at initial consultation. No mutations in ACT drug resistance markers were detected, although pfcrt-pfmdr1 haplotypes associated with lumefantrine tolerance were common. CONCLUSIONS: The upward trend in imported malaria, the substantial proportion of severe cases and the emergence of ACT failures are sources of concern, although late failures were infrequent. Genetic analysis did not support parasitological resistance to ACT, suggesting prospective pharmacokinetic studies should assess adequacy of partner drug dosage and duration of treatment in non-immune populations.

Molecular characterization of Staphylococcus aureus bloodstream isolates collected in a Dutch University Hospital between 1999 and 2006.

We observed that, between 1999 and 2006, up to 50% of the methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream isolates in our hospital had a genetic background common to endemic methicillin-resistant S. aureus clones (clonal complex 5 [CC5], CC8, CC22, CC30, and CC45). Furthermore, several successful MSSA lineages, such as CC7 and CC15, were observed.

Evaluation of the CellaVision DM96 advanced RBC application for screening and follow-up of malaria infection.

CellaVision DM96 is a digital cell morphology system for automated classification of white and red blood cells. CellaVision Advanced RBC application (ARBCA) pre-classifies RBC in 21 categories, including parasitized RBC, and allows re-classification by the operator. In this study, the performance of the software for detection of malaria and calculation of parasitemia was evaluated and compared to microscopy (n=40). For CellaVision, both pre- and post-reclassification results were evaluated. Sensitivity was moderate, even post-reclassification (72%), due to low numbers of analyzed RBC and limited resolution of photographs. CellaVision results correlated with microscopy according to Passing-Bablok analysis, with slightly lower values for CellaVision. Within-run, between-run and inter-observer variability were acceptable. The low sensitivity of CellaVision ARBCA precludes its use as a screening technique for malaria. However, due to its good correlation with microscopy and short turn-around-times, it may be useful in follow-up of parasitemia. Larger studies are required to confirm these findings.

Post-influenza aspergillosis, do not underestimate influenza B.

Our objective is to highlight and focus on post-influenza aspergillosis, triggered by influenza B virus. This relatively new clinical entity is often associated with a fulminant course of respiratory decline and high mortality. A 51-year immunocompetent woman, without any medical history or risk factors for developing a complicated influenza infection, was admitted to the intensive care unit. During admission, she presented with an afebrile flu-like syndrome, myocarditis, rhabdomyolysis, multiple organ failure, and evolved to severe respiratory distress. The broncho-alveolar lavage contained influenza B RNA, and the culture revealed Aspergillus fumigatus. Despite maximal organ support, immunoglobulin, antiviral and antifungal therapy, the patient died. This case demonstrates that influenza B virus may be life threatening even to immunocompetent adults and may trigger an invasive Aspergillus superinfection.

Nontuberculous mycobacteria among pulmonary tuberculosis patients: a retrospective Belgian multicenter study.

OBJECTIVES: Currently, there are no European data about the frequency and clinical significance of nontuberculous mycobacteria (NTM) grown from respiratory samples during the treatment of tuberculosis (TB). We determined the frequency and clinical significance of NTM isolated before or during pulmonary tuberculosis treatment in Belgian laboratories. METHODS: We conducted a nationwide retrospective multicenter cohort study on the co-isolation of TB and NTM in Belgium. Starting from laboratory data between 2006 and 2013, possible TB-NTM co-isolations were searched for. RESULTS: A total of 2569 unique culture-positive pulmonary tuberculosis cases were included in the study. Only 35 (1.4%) of these TB cases had an NTM co-isolated, and two of these 35 fulfilled the ATS criteria for NTM lung disease. CONCLUSION: A very low prevalence of 1.4% NTM co-isolations was found in Belgian patients with culture-proven pulmonary TB.

Alternaria infectoria phaeohyphomycosis in a renal transplant patient.

A male renal transplant patient developed a tumor on the dorsum of his right hand. After excision, histological examination of the tumor showed hyphal structures, but growth developed very slowly. Therapy consisted of surgery alone. A definitive identification of Alternaria infectoria was only possible with molecular techniques.

Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole.

A case of Scedosporium apiospermum keratitis was successfully treated with oral voriconazole and penetrating keratoplasty. Voriconazole levels in the aqueous humor were 53% of the levels in plasma and exceeded the MIC for the isolate by sevenfold.