Hospital and U.S. Navy medical providers work together to transfer the first of five COVID-19 positive patients to the expanded post-anesthesia care unit at the Northern Navajo Medical Center, Shiprock, NM, in December. The additional nurses and modifications free up the intensive care unit for hospital staff to treat non-COVID patients in need of critical care. Army photo by Maj. Bonnie Conard

TRENTON, NJ — Hospitals across the country have improvised intensive care units, converted garages into wards and increased the number of patients under each clinician’s care as a flood of COVID-19 patients washes away established protocols and practices. In the effort to survive the deluge, all available personnel have shifted to patient care in many facilities, pushing infection prevention, quality control and environmental control to the side.

In May, a similar surge of patients and redirection of staff at a New Jersey hospital created fertile ground for an outbreak of carbapenem-resistant Acinetobacter baumanii (CRAB), a nasty pathogen of keen interest to the DoD.

“During conflicts in the Middle East, military members were infected with a highly resistant bacterium, Acinetobacter baumannii,” said Navy Capt. Guillermo Pimentel, PhD, chief of the DoD’s Global Emerging Infections Surveillance (GEIS) Program, a branch of the Armed Forces Health Surveillance Division within the Defense Health Agency. “The complexity of these infections caused longer recovery times and often resulted in catastrophic disability.”

While GEIS has historically focused on monitoring antibiotic resistance in different regions of the world and tracking the movement of antibiotic resistant genes as part of its mission to protect deployed service members, its skills and the developments of its partner agencies within DoD could well be needed Stateside this winter.

The New Jersey Experience

In December, the U.S. Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report discussed the New Jersey outbreak and the implications for other hospitals managing a crush of COVID-19 patients.1

Acinetobacter baumannii is a leading cause of hospital-acquired infections worldwide. The World Health Organization (WHO) classifies CRAB as a priority 1 or critical pathogen for the development of new antibiotics and it’s number one on the U.S. CDC list of “urgent threat” pathogens.

In the United States, nearly half of Acinetobacter baumannii organisms demonstrate resistance to carbapenem. CRAB readily spreads in the hospital environment, on providers’ hands, and by asymptomatic individuals. It also persists for long periods on dry surfaces. In the best of times, these factors make controlling CRAB outbreaks challenging.

Between February and July 2020, 34 patients in a New Jersey hospital developed hospital-acquired infections or colonization with multidrug-resistant (MDR) CRAB. Nearly two-thirds of them were admitted to two intensive care units for COVID-19 patients.

“In late March, increasing COVID-19–related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices,” wrote Stephen Perez, of the CDC’s Epidemic Intelligence Service in Atlanta, and colleagues at the CDC, New Jersey Department of Health in Trenton, NJ, and New Jersey Medical School at Rutgers University in Newark, NJ.

A number of other institutions around the world also experienced an increase in multidrug resistant organisms (MDROs) as they responded to a rapid rise in SARS-CoV-2 infections and hospitalizations that exceeded their staffing and physical capacity.

“During COVID-19 preparations and the ensuing surge in cases, decreased vigilance for control of CRAB transmissions, including suspension of the MDRO workgroup, reduced surveillance cultures, reduced personnel numbers (which decreased capacity for overall auditing practices), and both intentional and unintentional changes in IPC practice likely contributed to this CRAB cluster,” the authors noted. Facilities facing similar challenges as the pandemic progresses should emphasize infection prevention and control to the extent possible and return to IPC best practices as quickly as possible.

DoD Seeks to Expand Armamentarium

The rising number of patients hospitalized with COVID-19 and Acinetobacter baumannii could create a situation where two whole-of-government responses—Operation Warp Speed (OWS) and the National Action Plan for Combating Antibiotic Resistant Bacteria (CARB)—intersect.

The DoD, which sent medical personnel to help overwhelmed hospitals, became involved with helping them fight resistant infections.

GEIS and the Walter Reed Army Institute of Research Multidrug-resistant Organism Repository and Surveillance Network (MRSN) have built an extensive resistance tracking system along with a standardized genomic characterization of MDROs. For Acinetobacter baumannii specifically, the MRSN has developed a 100-strain diversity panel that includes a wide range of phenotypes, antibiotic susceptibility/resistance characteristics, and more than 100 gene alleles associated with resistance. The panel provides the most diverse, well documented, and comprehensive set of Acinetobacter baumannii strains available for use by industry, academia, federal agencies, and other laboratories at no cost to aid the development of solutions to increasing resistance in pathogens.

Encouraging development of new antibiotics and other treatments for Acinetobacter baumannii is crucial, in large part because of its natural characteristics. “Of all the bacterial species found on the planet, relatively few are intrinsically multidrug-resistant pathogens,” said Army Col. Michael Zapor, MD, an infectious disease physician at Walter Reed National Military Medical Center in Bethesda, Maryland. “In Iraq and Afghanistan, the bacterium known as Acinetobacter is one such MDR bacterium that has caused problems in our patient population.”

In response, Army researchers developed one antibiotic that can treat several extremely MDRO pathogens. Arbekacin, a semisynthetic aminoglycoside, was initially approved by the U.S. Food and Drug Administration to treat methicillin-resistant Staphylococcus aureus (MRSA) but has also shown effectiveness against multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii.

In addition, the DoD provided a $3 million grant in 2019 to Appili Therapeutics to develop its novel AT1-1503 antibiotic program on the negamycin scaffold, which has gram-negative antibacterial abilities. The program will target particularly resistant organisms that cause many nosocomial infections, the so-called ESKAPE group of pathogens. The ESKAPE group includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.

 

  1. Perez S, Innes GK, Walters MS, et al. Increase in Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions — New Jersey, February–July 2020. MMWR Morb Mortal Wkly Rep 2020;69:1827–1831.