Top Infectious Disease News of the Week—August 18, 2019

#5: Controlling Legionella: Discussions from the HITS Consortium

The Healthcare Infection Transmission Systems (HITS) Catalyst for Change conference was recently held in Buffalo, New York. The 3-day consortium focused on several topics, with 1 day especially focused on the health care burden and control efforts for Legionella. The causative bacteria of Legionnaires’ disease poses a unique public health threat and continues to cause outbreaks, with a large one recently reported in Atlanta, Georgia. Legionella is also extremely problematic for health care facilities, as it can easily prey on immunocompromised patients if proper water management protocols are not followed.

The final day of the consortium was focused on Legionella and water safety measures in health care, with discussions led by speakers Janet Stout, PhD; Sarah Clock, MPH, PhD; and Molly Scanlon, PhD, FAIA, FACHA. The speakers asked several key questions and discussed many difficult topics for health care professionals, with a focus on whether Legionnaires’ disease can be stopped.

For one, Stout emphasized that potable water is the most important source of Legionella transmission and that cooling towers are actually not a common source for sporadic or health care-associated cases, but rather large community outbreaks. Perhaps the most daunting statistic presented was that health care facilities account for 57% of Legionella cases and 85% of deaths.

Read the recap of the HITS Consortium.

#4: Pharmacomicrobiomic Study Shows Significant Gut Bacteria Role in Drug Metabolism and Exposure

There is an increasing awareness of the potential role that the gut microbiota can play in drug metabolism, drug exposure, and drug action. Orally administered drugs typically encounter gut microorganisms prior to absorption and recent studies have shown that, in some cases, these bacteria possess drug-metabolizing capabilities that can significantly influence clinical drug exposure, activity, and toxicity. Examples of such include the metabolism of omeprazole by gut anaerobes,¹ microbiota-mediated metabolism of lovastatin precipitated by antibiotic co-administration,² and the reduction of digoxin by a specific gut organism.³ This has led to the emergence of a new field of study that has strong potential to inform personalized medicine—pharmacomicrobiomics.⁴ Defined as a sub-discipline intersecting microbiology, genomics, and pharmacology, pharmacomicrobiomics studies the effects that the human microbiome has on drug exposure, activity, and toxicity. However, the field is relatively new and although there have been several reports of microbial biotransformation, there have been few in-depth investigations into the specificity of bacterial strains or the chemical determinants that may predict drug transformations.

A recent study by Zimmerman, et al. provides what may be the first in-depth examination of the molecular mechanism of biotransformation of a large number of orally administered agents by the human gut microbiota.⁵ The study surveyed the metabolic activity of 76 human gut bacteria, representing the major phyla of the human gut microbiome, against 271 oral drugs. High-throughput genetic analysis coupled with mass spectrometric methods was used to identify the bacterial gene products responsible for drug metabolism and the specific metabolic reaction. The investigators showed that after a 12-hour incubation period, two-thirds of the analyzed drugs were metabolized to a significant extent (>20%) by at least 1 of the bacterial strains investigated. They further showed that each bacterial strain that was studied metabolized between 11 and 95 drugs. Importantly, the investigators were able to identify phylum-specific metabolic activities by clustering the drug-metabolizing activities of the bacterial isolates. They reported that drugs containing ester or amide functionalities were specifically susceptible to metabolism by the Bacteroidetes, while other organisms showed a preference for nitrogen-containing functional groups.

Read our latest In the Literature web article.

#3: Combination Therapy for MRSA Bloodstream Infections: Still a Question Mark

The addition of a β-lactam to a daptomycin regimen for patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections was associated with significantly reduced odds of clinical failure in a retrospective, comparative cohort study. But acute kidney injury was more common in the combination arm, indicating that additional research is still necessary.

The question of combination therapy versus monotherapy for MRSA bloodstream infections is one that is widely debated. In this new analysis, a team of investigators from Wayne State University and the University of California at San Francisco conducted research at 2 academic medical centers between 2008 and 2018. The results were published recently in Clinical Infectious Diseases.

“Combination of vancomycin or daptomycin with a β-lactam has been shown in vitro to be synergistic and has the potential to decrease the emergence of resistance in S aureus,” Michael J. Rybak, PharmD, MPH, PhD, professor of pharmacy & medicine at the Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy & Health Sciences at Wayne State University, and co-author on the study, told Contagion® of the motivation behind the research.

Read about combination therapy for MRSA bloodstream infections.

#2: First Phase 1 Trial of Chlamydia Vaccine Candidate Shows Promising Results

The US Centers for Disease Control and Prevention (CDC) estimates that the rate of sexually transmitted infections (STI) are on the rise with an estimated 1.7 million cases documented in 2017 in the United States.

Although chlamydia can typically be successfully treated with antibiotics, if left untreated it can cause serious health issues. Untreated chlamydia in women can cause severe damage to the uterus and fallopian tubes and lead to and ectopic pregnancy in women or even infertility.

With the rate of cases on the rise, it is clear that screening programs and antibiotic treatment alone have fallen short in decreasing incidence. Furthermore, there are no vaccines available to prevent against the infection.

Read about the first phase 1 chlamydia vaccine trial.

#1: FDA Approves Lefamulin for Community-Acquired Bacterial Pneumonia

The US Food and Drug Administration (FDA) has approved lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia (CABP) after results from 2 phase 3 studies showed the novel pleuromutilin antibiotic to be non-inferior to existing treatment options.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease,” said Ed Cox, MD, MPH, director of FDA’s Office of Antimicrobial Products in a statement issued by the FDA. “For managing this serious disease, it is important for physicians and patients to have treatment options. This approval reinforces our ongoing commitment to address treatment of infectious diseases by facilitating the development of new antibiotics.”

In total, the efficacy of lefamulin was evaluated in 1289 patients with CABP. In the LEAP 1 trial, IV to oral lefamulin was found to be non-inferior to IV to oral moxifloxacin with or without linezolid. In LEAP 2, lefamulin again successfully met the FDA primary endpoint of non-inferiority compared with moxifloxacin for early clinical response, which was evaluated in the intent-to-treat patient population 72 to 120 hours after treatment was initiated.

Lefamulin was shown to be well-tolerated with a favorable safety profile and can be dosed orally without regard to food, according to Jennifer Schranz, MD, chief medical officer with Nabriva Therapeutics.

“Lefamulin has benefits over other antibiotics for community acquired pneumonia. First, lefamulin is a new class of antibiotics. It’s a semi-synthetic derivative of this class called pleuromutilins, which is a derivative of a natural product—an oyster mushroom,” Schranz told Contagion® in an interview at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2019).

Read about the FDA approval of lefamulin.