July 360: Trending Infectious Disease News of the Month

If the summer months are intended for rest and relaxation, the infectious disease community clearly did not get the memo as July proved to be yet another busy news month.

Some of the biggest news of the month was presented at the 10^th IAS Conference on HIV Science (IAS 2019) held from July 21-24 in Mexico City, Mexico. Conference highlights included new data on a switch to dolutegravir/lamivudine, including 48-week data from the TANGO study and 96-week results from the GEMINI trial. The results of the phase 2a ASCENT study support the use of a bivalent clade C-Mosaic1 gp140 with Ad26.Mos4.HIV vaccine, which will be evaluated in the upcoming phase 3 Mosaico study.

Additionally, more data was presented on the link between dolutegravir use during pregnancy and neural tube defects. Based on these findings, the World Health Organization (WHO) announced updated recommendations on first- and second-line antiretroviral therapy, including dolutegravir. Under this update, the WHO now recommends the use of dolutegravir as the preferred first-line and second-line treatment for all populations, including pregnant women and those of childbearing potential.

In US Food and Drug Administration news, imipenem/cilastatin + relebactam (Recarbrio) was approved for the treatment of complicated urinary tract infections and complicated intra-abdominal bacterial infections in adults who have limited or no alternative treatments available.

Following the approval, Contagion® spoke with Keith Kaye, MD, MPH, professor of internal medicine and director of research in the Division of Infectious Diseases at the University of Michigan Medical School, to discuss the implications of the approval. Kaye is also a principal investigator in Merck’s clinical program on IMI/REL and a member of the Contagion® Editorial Advisory Board.

The Ebola outbreak in the Democratic Republic will officially document its 1-year anniversary on Thursday, August 1^st. The outbreak reached a new milestone on July 17^th when the WHO International Health Regulations Emergency Committee convened for the fourth time to assess the threat level of this outbreak.

The committee voted that the outbreak should be seen as an international public health risk. WHO director-general Tedros Adhanom Ghebreyesus, PhD, accepted the recommendation and officially declared the outbreak a public health emergency of international concern.

Back in the United States, the US Centers for Disease Control and Prevention, along with the US Food and Drug Administration, announced 5 new infectious disease outbreaks: a Salmonella outbreak linked to papaya; an E coli outbreak that turned deadly for 1 child and was tied to a petting zoo at the San Diego County Fair; a zoonotic Salmonella outbreak associated with pig ear dog treats; an outbreak of Cyclospora linked to fresh basil from Mexico that has sickened more than 100 individuals; and an E coli outbreak with a suspected link to consumption of ground bison.

Measles cases in the United States are appearing to slow after a record-breaking year. The highest number of weekly measles cases was documented during the week ending on March 23, 2019, during which 87 new cases of measles were confirmed. In comparison, during the week ending on July 25, 2019, only 16 new cases were documented.

For case counts on all of these infectious disease outbreaks, be sure to check out the Contagion® Outbreak Monitor.

Looking to learn more about utilizing methicillin-resistant Stapylococcus aureus nasal screening in antimicrobial stewardship? Be sure to check out this month’s In the Literature article authored by Krutika N. Mediwala, PharmD, BCPS, BCIDP from the Medical University of South Carolina.

Let’s take a look at the top 5 web articles from the month of July:

5. US Measles Cases Taper Off After Record-Breaking Year

After a worrisome first half of the year, new measles cases in the United States have begun to slow, according to new figures released by the US Centers for Disease Control and Prevention (CDC).

Measles has been a cause for concern for parents, clinicians, and public health officials alike as the vaccine-preventable disease has made a resurgence in the United States in 2019. On April 24, 2019, the United States officially documented the greatest number of measles cases in a given year since the disease was declared eliminated in 2000.

As of July 3, 2019, there have been 1109 cases of measles confirmed across 28 states in 2019. This figure is nearly 3 times the cumulative number of cases confirmed in 2018.

Read about the current state of the measles outbreak.

4. Utilizing MRSA Nasal Screening for Antimicrobial Stewardship

Highlighted Study:

Carr, AL, Daley, MJ, Givens Merkel, K, Rose, DT. Clinical utility of methicillin-resistant staphylococcus aureus nasal screening for antimicrobial stewardship: a review of current literature. Pharmacotherapy. 2018 Dec;38(12):1216-1228. doi: 10.1002/phar.2188. Epub 2018 Oct 29.

Staphylococcus aureus is a common pathogen in health care-associated infections (HAIs).¹ Upwards of 40% of deep-seated S aureus infections confer methicillin-resistance. Patients with methicillin-resistant S aureus (MRSA) bacteremia and endocarditis may carry a mortality rate of 40%.^1,4 Current guidelines from the Infectious Diseases Society of America (IDSA) recommend empiric MRSA coverage in patients with certain risk factors.^2-6 Even without risk factors, most patients receive empirical vancomycin therapy. MRSA nasal screening, with clinical context, can be utilized to prevent unnecessary exposure, adverse events, and increased expense. ⁷ MRSA colonization can be detected via culture (1-3 days; 86.9% sensitivity) or polymerase chain reaction (PCR) (<1 day; 92.5% sensitivity). ^8,9 The prevalence of MRSA directly impacts the performance of the nasal screen in predicting clinical MRSA infection. A higher prevalence will result in lower negative predictive value. This systematic review by Carr et al., summarized available literature on adult inpatients for whom MRSA nasal swab screening was conducted.¹⁰

Read about evidence by infection type

3. Pan-resistant, Currently Untreatable Gram-Negative Infections Come Closer to Home

The global emergence of antimicrobial resistance among gram-negative (GN) species is a major public health concern. This year the US Centers for Disease Control and Prevention reported multiple cases of pan drug-resistant (PDR) Pseudomonas aeruginosa originating from a bariatric surgery clinic in Tijuana, Mexico, prompting the agency to issue travel warnings. Organisms were isolated from 10 patients across 2 states, and effective therapeutic options were very limited. As pan-resistant infections have become a reality, clinicians face an increasing dilemma with how to treat multidrug-resistant strains.

The first US case of pan-resistant bacteria was reported by McGann et al, which identified an Escherichia coli strain isolated from a urine culture in which both mcr-1 and bla_CTX-M were present on a novel IncF plasmid, resulting in resistance to both colistin and β-lactamase.

A 2016 case of pan-resistant Klebsiella pneumoniae was documented in the US in a woman who had recently arrived from India and was admitted to a Nevada hospital with SIRS. A K pneumoniae strain isolated from her hip abscess was shown to be resistant to all 26 antimicrobials tested, including B-lactams, colistin, and aminoglycosides (Table). Tigecycline demonstrated intermediate activity against this strain, but the patient died from septic shock within 1 month.³ Whole genome sequencing of the isolate revealed a 5.4Mb chromosome and 3 plasmids belonging to multi-locus sequence strain (ST)15, and 4 β-lactamase genes: 2 chromosomal extended-spectrum β-lactamase (ESBL) (bla _CTX-M-15 and bla _SVH-28) and 2 plasmid borne elements (the carbapenemase bla _NDM-1 and class C B-lactamase bla _CMY-6.). Genetically conferring resistance to all tested β-lactams and β-lactamase inhibitors.

Read about the rise in pan-resistant infections.

2. FDA Approves Imipenem/Cilastatin + Relebactam

The US Food and Drug Administration has approved imipenem/cilastatin + relebactam (Recarbrio) for the treatment of complicated urinary tract infections and complicated intra-abdominal bacterial infections in adults who have limited or no alternative treatments available.

A new drug application (NDA) was accepted in February for the combination of relebactam, Merck’s investigational beta-lactamase inhibitor, with imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) caused by certain susceptible gram-negative bacteria.

Recarbrio is indicated in patients 18 years of age and older who have limited or no alternative treatment options, for the treatment of cUTI, including pyelonephritis, caused by the following susceptible gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa. It is also indicated for the treatment of cIAI caused by the following susceptible gram-negative microorganisms: Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis and Pseudomonas aeruginosa.

Read about the approval for cUTI and cIAI.

1. Sounding Off: Dr. Drew on How LA's Homeless Problem Is a Public Health Emergency

Drew Pinsky, MD, cannot understand how the situation on the Pacific Coast, and Los Angeles, in particular, is being tolerated.

“It’s beyond anything that is sustainable or rational or morally allowable,” he said of the humanitarian crisis that’s driving a rise in infectious diseases there.

Contagion® recently spoke with Pinsky, an internist, addiction medicine specialist, and prominent media personality, about the situation out West, what contributing factors are at play, and how health care providers can help.

Read the full Q&A with Dr. Drew.