Jonna Lorenz

Hospital exposure to antibiotics associated with 

 were linked to a greater risk of multidrug-resistant organisms (MDRO) in nursing home patients and environments, according to research presented during IDWeek 2020.

A team of investigators from the University of Michigan set out to examine the effects of hospital-based antimicrobial stewardship programs on nursing homes. Those involved in the research included Kyle Gontjes, MPH; Kristen Gibson, MPH; Bonnie Lansing, LPN; Karen Jones, MPH, RN, CIC; Marco Cassone, MD, PhD; Joyce Wang, PhD; John Mills, MD; Lona Mody, MD, MS; and Payal Patel, MD, MPH.

“Exposure to high-risk ‘C. diffogenic’ antibiotics, those that markedly increase the risk of 

 infection in the hospital, led to the recovery of multidrug-resistant organisms in nursing home patients and their environment,” the authors told 

®. “Therefore, treatments given in the hospital have a downstream impact on patients and their environment in the nursing home.”

The study included 618 post-acute care patients in 6 nursing homes between 2013 and 2016. Patients and high-touch surfaces were screened for methicillin-resistant 

(MRSA), vancomycin-resistant enterococci (VRE), and resistant Gram-negative bacilli (rGNB). Results were analyzed to determine whether hospital exposure to C. diffogenic agents — fluoroquinolones, third- and forth-generation cephalosporins, penicillin combinations, lincosamides, and carbapenems — was an independent risk factor for MDRO.

“Antibiotic exposure prior to nursing home arrival was common in our post-acute care patient population,” the authors said. “We identified that approximately 60% post-acute care patients had an antibiotic exposure prior to study enrollment upon arrival to the nursing home. Interestingly, when looking at the types of antibiotics prescribed to these patients, we identified that approximately 66% of these patients received an antibiotic that may have placed them at an increased risk of

MDRO patient colonization was identified on 350 patients (56.6%), including 98 with MRSA, 208 with VRE; and 196 with rGNB. MDRO contamination was present in 68% of patient rooms, including 166 with MRSA, 293 with VRE, and 182 with rGNB.

Hospital exposure to C. diffogenic antibiotics was an independent risk factor for MDRO patient colonization (OR, 1.94; 95% CI, 1.35-2.79) and MDRO environment contamination (OR, 1.94; 95% CI, 1.43-2.63), VRE patient colonization (OR, 4.23; 95% CI, 2.59-6.90), and VRE environment contamination (OR, 2.58; 95% CI, 2.00-3.33), the study found.

Clinicians and health care providers should be aware that antibiotic prescribing during the patient’s hospital stay can have a long-term impact on their health, including during their nursing home stay,” the authors said. “Additionally, hospital antibiotic prescribing can indirectly influence the patterns of multidrug-resistant organisms in nursing homes.

“Globally, our data supports investigating the potential value of migrating from being siloed, independent actors in antimicrobial stewardship to forming integrated stewardship partnerships between hospitals and their preferred nursing homes.”

More research is needed to better understand how hospital and nursing home antibiotic exposures affect MDROs and whether antimicrobial stewardship program interventions may influence outcomes.

 presented at IDWeek found that patient colonization and environmental contamination with a variety of MDROs was common among a group of 45 patients admitted to the intensive care unit.

 detailing steps clinicians can take to to address antibiotic resistance.

More than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.

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Hospital Exposure to Antibiotics Associated with C diff Pose Higher Risk of MDRO 

At least 10% of patients with life-threatening coronavirus diseases 2019 (COVID-19) pneumonia have antibodies that attack their own interferons, according to a new study by a team of international investigators.

, found that 101 out of 987 patients with severe COVID-19 pneumonia had IgG autoantibodies that neutralize the ability of type 1 interferons to block SARS-CoV-2 infection.

“This was a huge surprise, much unexpected,” corresponding author Paul Bastard, affiliated with Inserm, University of Paris Imagine Institute and St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University, told 

®. “Very surprising how it mimics genetic inborn errors of immunity. Extremely surprising too that individuals with complete genetic defects in key interferon genes (as described in Zhang Q and al., Science, 2020) were adult patients who had not suffered previously from severe viral infections.”

, the team detailed genetic variants contributing to life-threatening COVID-19 pneumonia. Loss-of-function variants at 13 human loci known to govern TLR3- and IRF7-dependent type 1 interferon immunity to influenza virus were examined. Genetic defects leading to impaired production or response to type 1 interferons were reported in 23 patients (3.5%).

The twin studies come from lab of Jean-Laurent Casanova, MD, PhD, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at the Rockefeller University, and the COVID Human Genetic Effort, a international collaboration aiming to determine how human genetics determine severe COVID-19.

The antibody study included 987 patients with critical COVID-19, 663 asymptomatic or pauci-symptomatic patients with COVID-19, and 1227 healthy controls. Autoantibodies were found in none of the patients with asymptomatic or mild COVID-19 and in only 4 of the healthy participants. Based on this, the estimated prevalence of these autoantibodies in the general population is 0.33%.

The study also could help explain why men have been more adversely affected by COVID-19 than women, finding that 95 of the 101 patients with the autoantibodies were men.

The neutralizing autoantibodies are believed to have been present before SARS-CoV-2 infection and caused the severity of the disease. They were identified in 2 patients before infection and 3 patients with APS-1, a serious but rare immune diseased marked by a high concentration of antibodies against interferons, had life-threatening COVID-19.

“It would be important to implement routine testing for auto-antibodies in all patients infected with COVID-19 to be able to implement adequate treatments and preventive measures. And perform genetic testing in the patients with unexplained severe COVID-19,” Bastard said.

Treatment could include early injected or nebulized IFN-β because autoantibodies that work against that type of interferon are rare among those affected, while treatment with IFN-α is unlikely to be affective, the study said.

Early intervention might be key. Once patients are hospitalized, it might be too late for treatment to show benefits. The World Health Organization 

 recently released results indicating that interferon-beta therapy didn’t lower mortality nor the need for ventilation among more than 2,000 people who received the drug.

Autoantibodies that attack type 1 interferons, neutralizing the immune system’s ability to block the SARS-CoV-2 virus, were present in 10% of patients with life-threatening coronavirus diseases 2019 (COVID-19) pneumonia, a new study found.

Autoantibodies Block Interferons in 10% of Severe COVID-19 Cases

Cefiderocol could be an important tool in the fight against multidrug-resistant gram-negative bacterial infections, according to a pair of recently released studies evaluating its efficacy and safety. But enthusiasm for the drug is tempered by lingering questions.

, were funded by Japanese pharmaceutical company 

, which launched the drug under the brand name Fetroja.

Cefiderocol is a cephalosporin that acts as a siderophore to penetrate the outer cell membrane of gram-negative pathogens.

“The best interpretation of cefiderocol that can be gleaned from these studies is that it is as good as comparator agents that are frankly suboptimal for the treatment of infections caused by carbapenem-resistant organisms,” Emily L. Heil, PharmD, of the University of Maryland School of Pharmacy, and Pranita D Tamma, MD, of Johns Hopkins Hospital, 

Drug-resistant pathogens are a global health concern, killing approximately 700,000 people each year.

APEKS-NP, a randomized, double-blind, phase 3, noninferiority trial, compared cefiderocol with high-dose extended-infusion meropenem for the treatment of gram-negative nosocomial pneumonia. It was led by Richard G. Wunderink, MD, of the Northwestern University Feinberg School of Medicine.

Cefiderocol was found to be noninferior in terms of the primary endpoint of all-cause mortality on day 14. Among patients who received cefiderocol, mortality was 12.4% (18 of 145 patients), compared with 11.6% (17 of 146) among those who received meropenem (adjusted treatment difference 0.8%, 95% CI-6.6 to 8.2; p=0.002).

 in 41. APACHE II scores of 16 or more were reported in 49% of patients, 60% of patients were mechanically ventilated, 68% were in intensive care units.

Treatment-emergent adverse events were reported in 130 (88%) of patients in the cefiderocol group and 129 (86%) of those in the meropenem group, with the most common being urinary tract infection and hypokalaemia respectively.

As a result of the APEKS-NP study, the U.S. Food and Drug Administration in September 

approved a supplemental New Drug Application

 for cefiderocol to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by gram-negative pathogens. Cefiderocol previously was approved for the treatment of complicated urinary tract infections caused by gram-negative pathogens.

CREDIBLE-CR, a randomized, open-label, multicenter, pathogen-focused, phase 3 trial, evaluated the safety and efficacy of cefiderocol compared with the best available therapy (BAT) to treat nosocomial pneumonia (NP), bloodstream infections (BSI), sepsis, and complicated urinary tract infections (cUTI) caused by carbapenem-resistant gram-negative infections. It was led by Matteo Bassetti, MD, head of the Infectious Diseases Clinic, San Martino Hospital, Genoa, Italy.

, Enterobacterales and metallo-beta-lactamase expressing organisms.

The study, which was conducted in 95 hospitals in 16 countries, found that cefiderocol had similar clinical and microbiological efficacy to best available therapy. The study included 28 different BAT regimens, with 71% (27/38) of cases using combination therapy, including 66% (25/38) with colistin. Cefiderocol treatment was a monotherapy in 83% (66/80) of cases.

The primary endpoint was clinical cure at test of cure at day 7 for NP, BSI and sepsis and microbiological eradication for cUTI. Among NP patients, clinical cure was achieved in 20 of 40 (50%) in the cefiderocol group compared with 10 of 19 (53%) in the BAT group. Among those with BSI or sepsis, clinical cure was achieved in 10 of 23 (43%) in the cefiderocol group compared with 6 of 14 (43%) in the BAT group. Among those with cUTI, microbiological eradication was achieved in 9 of 17 (53%) in the cefiderocol group and 1 of 5 (20%) in the BAT group.

Results for cefiderocol against infections caused by organisms producing metallo-β-lactamases (MBL) were substantially better than those of BAT, with clinical cure achieved in 12 of 16 (75%) compared with 2 of 7 (29%) respectively.

The CREDIBLE-CR study found that 28-day all-cause mortality was higher among patients treated with cefiderocol (25 of 101 patients, or 24.8%) than among those treated with the best available therapy (9 of 49 patients, or 18.4%). Mortality differences were notable in 

infections, which were present in 46% of patients. No mortality difference was observed among patients not infected with 

More research is needed to better understand the differences in mortality and to determine whether resistance to cefiderocol emerges.

“We remain optimistic that post-marketing data will allow for refinement of the drug’s place in therapy–hopefully broadening its indications,” Heil and Tamma wrote. “Until then it might be best to consider cefiderocol as a salvage option for patients with most multidrug-resistant gram-negative infections, except for those caused by MBL-producing Enterobacterales.

“Cefiderocol will be a valuable soldier in battles against gram-negative resistance but it probably will not win the war.”

Cefiderocol was noninferior to high-dose, extended-infusion meropenem in terms of all-case mortality in patients with gram-negative nosocomial pneumonia and showed similar clinical and microbiological efficacy to best available therapies in carbapenem-resistant, gram-negative bacterial infections, according to 2 recently released studies.

Cefiderocol Shows Promise in Phase 3 Studies, But Questions Remain 

The vast majority of early cases of coronavirus disease 2019 (COVID-19) in Southern California came from Europe, according to a new study of genomic characteristics and transmission routes of patients with confirmed SARS-CoV-2 infections.

, examined SARS-CoV-2 isolates from 192 patients at Cedars-Sinai Medical Center in Los Angeles, California, taken from March 22 to April 15. Investigators found that 82% of isolates were similar to those originating from Europe compared with 15% that matched isolates from Asia.

“That was the biggest surprise. We went in with one assumption and it was the complete opposite,” study co-author Eric Vail, MD, Molecular Pathology Laboratory, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, told 

The first U.S. case of COVID-19 was reported in Seattle in January, with transmission of the virus coming from China, and investigators expected to see similar transmission routes in the Los Angeles outbreak. However, after viral genomes were sequenced and compared with isolates from New York, Washington state and China, investigators discovered that most of the Los Angeles isolates were similar to those from New York, which were seeded from Europe.

“This is the power of science. You come in with an assumption and you can have that completely made wrong and it’s still interesting,” Vail said. “It’s more exciting sometimes to find out that what you were thinking was wrong than what you were thinking was right. I really appreciated that about this.”

Genomic sequencing can help epidemiologists track sources of transmission and evolution of the virus. The research also unveiled trends in hot spots, revealing nursing home spread, hospital spread and close-knit community spread.

High genomic diversity was observed, with a total of 518 variation sites detected across the length of the SARS-CoV-2 genome. Investigators tracked genome differences by constructing a phylogenetic tree and identified clusters of cases that originated from the same branching point. Among the cases were a cluster of 10 linked to skilled nursing facilities and health care workers, community transmission among a cluster of 13 patients in a small area, and person-to-person transmission in a cluster of 5 patients who shared the same single-nucleotide variation in their SARS-CoV-2 genomes.

“I think the genomic studies like this are a useful tool in the chest for epidemiologists,” Vail said. “Obviously contact tracing, traditional histories, things like that are still very important, but having the ability to confirm those findings with the genetics and be able to grow the tree so to speak and see where these things came from is also very useful. I think it’s also useful from a public health standpoint for future pandemics. Knowing how the spread happened is helpful from a public health perspective in trying to prevent things from happening like this in the future.”

Investigators didn’t find evidence of coinfection with other respiratory viral pathogens, which is consistent with earlier research.

Limitations of the study included that the isolates were all from patients who were hospitalized and didn’t represent the high incidence of cases that were asymptomatic or with mild symptoms. The study also can’t rule out the possibility that seed events occurred simultaneously in Europe, New York and California. It’s possible that European travelers seeded New York and Los Angeles simultaneously or that clusters of similar variants came from different locations.

Still, investigators concluded that it is likely that most samples from the study spread from multiple introductions from New York.

Vail said further research will examine the interaction of human genetics and viral genetics and how genetic factors may impact severity of disease.

A new study found most early cases of SARS-CoV-2 infection in Southern California were seeded from Europe rather than Asia, thus shedding light on how the pathogen spread in the United States.

Author | Jonna Lorenz

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