Safe shortening of antibiotic treatment duration for complicated bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

Introduction: A major knowledge gap in the treatment of complicated bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.

Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

Background: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH.

Methods And Findings: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.

Improving indicator-condition guided testing for HIV in the hospital setting (PROTEST 2·0): A multicenter, interrupted time-series analysis.

Background: Indicator-condition (IC) guided HIV testing is a feasible and cost-effective strategy to identify undiagnosed people living with HIV (PLHIV), but remains insufficiently implemented. We aimed to promote IC-guided HIV testing in seven ICs.

Methods: Relevant departments in five hospitals of the Amsterdam region participated.

Fosfomycin Vs Ciprofloxacin as Oral Step-Down Treatment for Escherichia coli Febrile Urinary Tract Infections in Women: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial.

Background: We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women.

Methods: This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2-5 days of empirical intravenous antimicrobials for E.

Good clinical outcome in a case of Listeria-associated multiple liver abscesses and clinical hepatitis.

This case report describes a patient with the rare phenomenon of multiple liver abscesses and signs of hepatitis, secondary to disseminated listeriosis. All signs and symptoms resolved with antibiotic treatment only, contradicting current literature. This suggests that the development of multiple liver abscesses following infection with Listeria monocytogenes does not necessarily yield a poor prognosis, even without drainage.

Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial.

Objectives: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis.

Methods: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital.

Effect of an antibiotic checklist on length of hospital stay and appropriate antibiotic use in adult patients treated with intravenous antibiotics: a stepped wedge cluster randomized trial.

Objectives: Quality indicators (QIs) have been developed to define appropriate antibiotic use in hospitalized patients. We evaluated whether a checklist based on these QIs affects appropriate antibiotic use and length of hospital stay.

Methods: An antibiotic checklist for patients treated with intravenous antibiotics was introduced in nine Dutch hospitals in a stepped wedge cluster randomized trial.

[Lactococcus garvieae endocarditis].

Background: Lactococcus garvieae, a Gram-positive lactococcus with a short incubation period and high virulence, is a known fish pathogen responsible for serious outbreaks in both marine and freshwater aquaculture. The first human infection was documented in 1991. This is the first case report of L.

Human foetal hepatocytes: isolation, characterization, and transplantation.

Hepatocyte transplantation has become an alternative to orthotopic liver transplantation for the treatment of liver metabolic diseases. However, there is an increasing lack of donor organs and isolated mature hepatocytes are difficult to manipulate and cannot be expanded in vitro. It is therefore necessary to find alternative sources of hepatocytes, and different approaches to evaluate the therapeutic potential of stem cells of different origins are being developed.

The role of HGF on invasive properties and repopulation potential of human fetal hepatic progenitor cells.

Unlabelled: The success of hepatocyte transplantation has been limited by the low efficiency of transplanted cell integration into liver parenchyma. Human fetal hepatic progenitor cells (hepatoblasts) engraft more effectively than adult hepatocytes in mouse livers. However, the signals required for their integration are not yet fully understood.

High incidence of asymptomatic syphilis in HIV-infected MSM justifies routine screening.

Background: Recently, the incidence of syphilis has risen, mainly among men having sex with men (MSM), many of whom are coinfected with HIV. Current guidelines recommend at least yearly syphilis testing in this group. In this study, we assessed the yield of routine syphilis screening in outpatient HIV-patients.

Efficient hepatocyte engraftment in a nonhuman primate model after partial portal vein embolization.

Background: Hepatocyte transplantation could be an alternative to whole liver transplantation for the treatment of metabolic liver diseases. However, the results of clinical investigations suggest that the number of engrafted hepatocytes was insufficient to correct metabolic disorders. This may partly result from a lack of proliferation of transplanted hepatocytes.

Efficient ex vivo gene transfer into non-human primate hepatocytes using HIV-1 derived lentiviral vectors.

Background/aims: Lentivirus-mediated ex vivo gene therapy is becoming a promising approach for the treatment of liver metabolic disorders. However, the feasibility of this approach needs to be studied in large animal models. The purpose of this study was to evaluate the efficacy of ex vivo gene transfer into Macaca hepatocytes with two different HIV-1 derived lentiviral vectors.

Primate hepatic foetal progenitor cells and their therapeutic potential.

Transplantation of genetically modified or unmodified hepatocytes appears to be a less invasive alternative to liver transplantation. However, clinical trials performed for the treatment of metabolic deficiencies resulted in a partial and transitory correction due to an insufficient number of engrafted and functional hepatocytes. In vitro, adult hepatocytes do not proliferate and the lack of organ donors limits their availability.

Lipopolysaccharide binding protein-deficient mice have a normal defense against pulmonary mycobacterial infection.

Lipopolysaccharide (LPS) binding protein (LBP) facilitates the transfer of LPS of Gram-negative bacteria to the pattern recognition receptor CD14, resulting in activation of immunocompetent cells. LBP can also facilitate the binding of lipoarabinomannan, a major cell wall component of mycobacteria, to immune cells. To determine the role of LBP in the immune response to pulmonary Mycobacterium tuberculosis infection, LBP gene-deficient (-/-) and normal wild-type (WT) mice were intranasally infected with M.

Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts.

Transplantation of hepatocytes is a promising alternative to liver transplantation for the treatment of severe liver diseases. However, this approach is hampered by the shortage of donor organs and intrinsic limitations of adult hepatocytes. To investigate whether most of the hurdles faced with adult hepatocytes could be surmounted by the use of human fetal hepatoblasts, we have developed a method to isolate, transduce, and cryopreserve hepatoblasts from human livers at an early stage of development (11-13 weeks of gestation).

Platelet-activating factor receptor-deficient mice show an unaltered clearance of nontypeable Haemophilus influenzae from their respiratory tract.

Platelet-activating factor (PAF), a glycerophospholipid with proinflammatory properties, exerts its biological effects by interacting with the PAF receptor (PAFR) expressed on many different cell types. The PAFR specifically binds phosphorylcholine, the biologically active component of PAF. However, phosphorylcholine is also a component of the cell wall of nontypeable Haemophilus influenzae (NTHi).

LPS-binding protein-deficient mice have an impaired defense against Gram-negative but not Gram-positive pneumonia.

LPS-binding protein (LBP) can facilitate the transfer of cell wall components of both Gram-negative bacteria (LPS) and Gram-positive bacteria (lipoteichoic acid) to inflammatory cells. Although LBP is predominantly produced in the liver, recent studies have indicated that this protein is also synthesized locally in the lung by epithelial cells. To determine the role of LBP in the immune response to pneumonia, LBP gene-deficient (-/-) and normal wild-type (WT) mice were intra-nasally infected with either Streptococcus pneumoniae or Klebsiella pneumoniae, common Gram-positive and Gram-negative pathogens, respectively.

P38 mitogen activated protein kinase is involved in the downregulation of granulocyte CXC chemokine receptors 1 and 2 during human endotoxemia.

Chemokine receptors CXC receptor (CXCR) 1 and 2, and their ligands interleukin (IL)-8 and growth-related oncogene alpha (GRO alpha), are principal regulators of neutrophil activation and migration. To investigate the role of p38 mitogen activated protein kinase (MAPK) in the regulation of CXCR expression during an inflammatory response in vivo, 24 healthy volunteers received an intravenous injection with lipopolysaccharide (LPS) preceded (-3 hr) by a specific p38 MAPK inhibitor (BIRB 796 BS) at a high dose (600 mg) or a low dose (50 mg) or a placebo. The LPS-induced reduction of neutrophil CXCR 1 and 2 expression, as determined by fluorescence-activated cell sorter analysis, was inhibited in volunteers receiving the high dose of the p38 MAPK inhibitor.

Toll-like receptor 4 plays a protective role in pulmonary tuberculosis in mice.

Toll-like receptors (TLR) play an essential role in the innate recognition of microorganisms by the host. To determine the role of TLR4 in host defense against lung tuberculosis, TLR4 mutant (C3H/HeJ) and wild-type (C3H/HeN) mice were intranasally infected with live Mycobacterium tuberculosis. TLR4 mutant mice were more susceptible to pulmonary tuberculosis, as indicated by a reduced survival and an enhanced mycobacterial outgrowth.