Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis.

BACKGROUND: Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. METHODS: We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low. RESULTS: Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor-associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels. CONCLUSIONS: This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure.

Low-Risk Staphylococcus aureus Bacteremia Patients Do Not Require Routine Diagnostic Imaging: A Multicenter, Retrospective, Cohort Study.

BACKGROUND: Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. METHODS: We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. Primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both actual therapy administered and by linking a adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival and factors associated with the performance of diagnostic imaging. RESULTS: Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%), imaging findings during patient admission had been interpreted as metastatic infections that should extend treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-day relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; adjusted odds ratio, 0.749; 95% confidence interval, .373-1.504). CONCLUSIONS: Our study advocates risk stratification for the management of SAB patients. Prerequisites are follow-up blood cultures, bedside infectious diseases consultation, and a critical review of disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.

Empiric antibiotic therapy in early periprosthetic joint infection: a retrospective cohort study.

PURPOSE: Periprosthetic joint infection (PJI) is a devastating complication following total knee or total hip arthroplasty (TKA/THA). Appropriate empiric antibiotic treatment, initiated directly after debridement and implant retention (DAIR), is suggested to contribute to treatment success. The aim of this study was to describe the microbiology and the antibiotic susceptibility in early PJI to guide future empiric treatment in a region with a low incidence of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Consecutive patients who underwent DAIR within 3 months after primary unilateral TKA or THA between January 2011 and December 2018 were retrospectively identified from the hospital electronic health records. Data on causative pathogens, antimicrobial susceptibility and the number of post-operative days until cultures demonstrated bacterial growth were collected. RESULTS: One hundred and eleven early PJIs were identified of which 65 (59%) were monomicrobial and 46 (41%) polymicrobial. Among all isolated pathogens, Staphylococcus aureus (n = 53; 29%) was the most commonly identified pathogen in early PJI without any involvement of MRSA. 72% of PJIs were susceptible to vancomycin which could be increased to around 90% by adding gram-negative coverage. On the 5th postoperative day, bacterial growth was observed in 98% of cases. All gram-negative bacteria demonstrated positive tissue cultures on the 4th postoperative day. CONCLUSION: Vancomycin combined with ciprofloxacin or a third generation cephalosporin provided the highest antimicrobial coverage of all responsible pathogens identified in early PJI. Empiric treatment of gram-negative treatment can be safely terminated in the absence of gram-negative pathogens after 4 days of culturing in cases without preoperative antibiotic treatment.

Autochthonous Human Case of Seoul Virus Infection, the Netherlands.

Orthohantaviruses are a group of rodentborne viruses with a worldwide distribution. The orthohantavirus Seoul virus (SEOV) can cause hemorrhagic fever with renal syndrome in humans and is distributed worldwide, like its reservoir host, the rat. Cases of SEOV in wild and pet rats have been described in several countries, and human cases have been reported in the United Kingdom, France, Canada, and the United States. In the Netherlands, SEOV has previously been found in wild brown rats. We describe an autochthonous human case of SEOV infection in the Netherlands. This patient had nonspecific clinical symptoms of an orthohantavirus infection (gastrointestinal symptoms and distinct elevation of liver enzymes). Subsequent source investigation revealed 2 potential sources, the patient's feeder rats and a feeder rat farm. At both sources, a high prevalence of SEOV was found in the rats. The virus closely resembled the Cherwell and Turckheim SEOV strains that were previously found in Europe.

Treatment of calcium and vitamin D deficiency in HIV-positive men on tenofovir-containing antiretroviral therapy.

BACKGROUND: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate-containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. OBJECTIVE: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. METHODS: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. RESULTS: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. CONCLUSION: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency.

Short Communication: Prolonged COVID-19 Infection in a Patient with Newly Diagnosed HIV/AIDS.

A 38-year-old male patient presented to the emergency department with fever and dyspnea. Hospitalization was warranted and soon coronavirus disease 2019 (COVID-19) was diagnosed based on a positive SARS-CoV-2-PCR. Over the following weeks his condition gradually worsened, leading to admission at the intensive care unit. Because of unexplained weight loss before admission, a HIV screening was performed. HIV was confirmed and additional tests showed an undetectable CD4+ T cell count, alongside a number of co-infections. Convalescent plasma therapy, which has been shown to be effective in severe humoral immunodeficiency was tried, but was not effective. One week after the HIV diagnosis, antiretroviral therapy was started and finally, 3 months after the initial positive test and after partial recovery of cellular immunity, the COVID-19 virus was cleared. In the end, the patient made a full recovery. Our case demonstrates a prolonged COVID-19 infection in a patient with undiagnosed HIV with severely impaired cellular immunity.

Long-Term Impact of Calcium and Vitamin D Supplementation on Bone Density in HIV+ Patients with Documented Deficiencies.

To assess the efficacy of long-term calcium and vitamin D treatment on bone mineral density (BMD) in HIV+ patients on combined antiretroviral therapy (cART). A retrospective, single-center cohort study. Between March 2010 and July 2012, 268 HIV+ patients were screened for vitamin D and calcium deficiency. Those with proven vitamin D or calcium deficiency received supplementation according to a predefined protocol, and were offered further evaluation of BMD by dual-energy X-ray absorptiometry (DEXA). Calcium and vitamin D status and BMD were assessed at baseline (T0) and approximately one (T1) and 4-6 years (T2) later. Percentual change in BMD of the lumbar spine and hip was compared with reported rates of change in HIV+ patients on cART without standard calcium and vitamin D treatment. The prevalence of vitamin D deficiency and calcium deficiency was 46% and 43%, respectively. Thirteen percent of patients had secondary hyperparathyroidism at baseline. DEXA performed in patients with a deficiency revealed osteopenia in 40% and osteoporosis in 8% of patients. The expected long-term change in lumbar spine and hip BMDs at T2 was -0.7%, -1.5%, and -1.5%, respectively. The measured changes were +2.3%, -0.6%, and -0.6%, respectively. The difference between measured and expected rate of change was significant for the lumbar spine (3.0%, p < .05), but not for the hip. Long-term vitamin D and calcium supplementation improves lumbar spine BMD of HIV+ patients with osteopenia or osteoporosis and with proven calcium and/or vitamin D deficiencies. Screening and treatment are recommended to become part of regular care.

Zidovudine continuous infusion in an HIV-infected pregnant woman with a phobia of swallowing pills.

The authors report the difficulties of preventing mother-to-child transmission in a pregnant HIV-infected woman with a phobia of swallowing pills. After multiple attempts and just as many failures, the authors ended up with cART consisting of small tablets of nevirapine, lamivudine and a continuous intravenous infusion of zidovudine given via an elastomeric pump at home. This case demonstrates the difficulties that HIV physicians can encounter in pregnant women who have difficulties in swallowing tablets. In exceptional circumstances, continuous infusion of zidovudine may be an option, even in an outpatient setting.

[Cerebellar dysfunction due to pneumonia caused by Legionella pneumophila]. / Cerebellaire stoornissen door Legionella-pneumonie.

BACKGROUND: Legionnaires' disease is frequently complicated by extrapulmonary symptoms such as neurological abnormalities. Cerebellar disorders are rare, but can be long-lasting and disabling. CASE DESCRIPTION: A 57-year-old male developed severe cerebellar disorders such as dysarthria and ataxia after being hospitalized for pneumonia. Despite an extensive diagnostic work-up, no explanation for the cerebellar symptoms could be found. The patient was transferred to a rehabilitation facility. Repeated serological tests revealed infection with Legionella, which was most probably the cause of the cerebellar dysfunction. CONCLUSION: Cerebellar disorders are a rare complication of Legionnaires' disease. The pathogenesis is unknown. There is no diagnostic test that proves or excludes cerebellar involvement in an infection caused by Legionella. The treatment is supportive and recovery can take months or even years.