Top Infectious Disease News of the Week—Week of April 14, 2019

#5: Tom van der Poll, MD, PhD: Biomarker Guided Therapies for Sepsis

In a symposium at the European Congress for Clinical Microbiology and Infectious Diseases (ECCMID 2019), Tom van der Poll, MD, PhD, professor and chair of medicine at UMC Amsterdam, the Netherlands, gave a presentation on redefining the syndrome of sepsis based on the use of biomarkers.

At the conclusion of the presentation, van der Poll highlighted that the hosts' response to sepsis is made up of concurrent proinflammatory and immune suppressive reactions. Therefore, gene transcription signatures can be used to gain information into pathogenetic mechanisms, while allowing stratification of patients into homogenous groups, and providing biomarker-guided treatment selection and monitoring.

In an exclusive interview at ECCMID 2019, Contagion® sat down with van der Poll to learn more about his presentation and using biomarkers in the field of sepsis.

Watch the interview here.

#4: ASPECT-NP: Ceftolozane/Tazobactam Efficacious for Ventilated Nosocomial Pneumonia

As antibacterial resistance rates are on the rise among gram-negative bacteria such as Pseudomonas aeruginosa, novel treatment options are needed to treat infections such as nosocomial pneumonia.

Ceftolozane/tazobactam (Zerbaxa) is a combination treatment of an anti-pseudomonal cephalosporin, ceftolozane, and an extended-spectrum β-lactamase inhibitor, tazobactam.

Ceftolozane/tazobactam is approved by the US Food and Drug Administration and is indicated for the treatment of adult patients with complicated urinary tract infections, including pyelonephritis, caused by particular gram-negative organisms. When used in combination with metronidazole, it is indicated for the treatment of complicated intra-abdominal infections cause by specific gram-negative and gram-positive microogranisms.

Read about ASPECT-NP and watch the interview with Marin Kollef, MD.

#3: Can Gene Editing Tool CRISPR Dispense With HIV?

CRISPR, the gene-editing tool making waves in the medical community for its ability to cut out undesirable genes and potentially change the course of diseases, is being looked at as a possible way to eradicate stubborn reserves of non-drug-resistant HIV that elude antiretroviral medication (ART).

According to a team of investigators from the University of Pittsburgh, roughly 1 in 10 people with HIV have detectable HIV levels in their blood despite remaining diligent about their ART regimens. The investigators, presenting last month at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019), explained that cells called repliclones, or HIV-containing cells that replicate, may be the culprit. It’s known that many people who have detectable HIV levels in spite of taking ART harbor reservoirs of virus that seem impervious to medication. “The repliclones are a subset of the reservoir that is producing enough virus to be detected by routine clinical assays,” John Mellors, MD, professor and chief of the Division of Infectious Diseases in the University of Pittsburgh School of Medicine, holder of Pitt’s Endowed Chair for Global Elimination of HIV and AIDS, and an author of the study, told Contagion®. “[T]he cells in the reservoir are dividing, which passes along the genetic code to produce virus, thus creating daughter cells with the ability to produce the virus.”

Read about gene editing for HIV.

#2: Jose Arribas, MD, on the Challenges That Come With Long-Acting Injectables

The announcement of the results of the FLAIR and ATLAS studies at the Annual Conference on Retroviruses and Opportunistic Infections in March was a major step forward in the field of long-acting injectables for the treatment and management of HIV. But with advances come challenges.

Jose Arribas, MD, head of the Infectious Diseases Unit at La Paz Hospital in Madrid, Spain, sat down with Contagion® at the European Congress of Clinical Microbiology and Infectious Diseases in Amsterdam to discuss the challenges that lie ahead in the development and implementation of monthly long-acting regimens, and also what other treatments are in the pipeline.

Watch the interview here.

#1: CAMERA2: Combination Therapy for MRSA Bacteremia Effective but Linked to Higher Mortality, AKI Rates

In vitro, animal models, and observational studies in humans have demonstrated that combination therapy comprising vancomycin, the current standard treatment, with a β-lactam appears to be more effective than monotherapy in treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.

But results from the largest clinical trial to date have raised concerns over the effects of combination therapy on mortality and rates of acute kidney injury (AKI).

The CAMERA2 study, presented at the European Congress of Clinical Microbiology and Infectious Disease (ECCMID 2019), sought to evaluate combination therapy through an investigator-initiated randomized controlled trial of patients with MRSA bacteremia.

Between August 2015 and July 2018, the trial enrolled 352 participants across 27 sites in 4 countries (Australia, New Zealand, Singapore, and Israel) who were diagnosed with MRSA bacteremia within 72 hours of index blood culture draw, who were aged 18 years and older, and who were likely to remain an inpatient for ≥7 days. Participants were randomized to either the standard treatment, vancomycin or daptomycin, or the standard treatment plus an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin).

The primary endpoint was a composite outcome at 90 days of all-cause mortality, persistent bacteremia at day 5 or beyond, microbiological relapse, or microbiological treatment failure, and assessed by a blinded adjudication committee. Secondary endpoints included individual elements of the composite primary endpoint, bacteremia at day 2, and acute kidney injury or need for renal replacement therapy.

Two hundred fifty two of the participants were from New Zealand or Australia, 56 from Singapore, and 44 from Israel. The median age of participants was 64 years, 34% were female, and 64% had a health care-associated infection. Fifteen percent were receiving haemodialysis. Three hundred forty four participants (standard care n = 174, combination n = 170) were included in the modified intention-to-treat analysis. The trial was stopped early on the recommendation of the data and safety monitoring board.

Read about CAMERA2 and watch the interview with Steven Tong, PhD.