key: cord-299699-9uiv3n41
authors: Nori, Priya; Szymczak, Wendy; Puius, Yoram; Sharma, Anjali; Cowman, Kelsie; Gialanella, Philip; Fleischner, Zachary; Corpuz, Marilou; Torres-Isasiga, Julian; Bartash, Rachel; Felsen, Uriel; Chen, Victor; Guo, Yi
title: Emerging Co-Pathogens: New Delhi Metallo-beta-lactamase producing Enterobacterales Infections in New York City COVID-19 Patients
date: 2020-09-25
journal: Int J Antimicrob Agents
DOI: 10.1016/j.ijantimicag.2020.106179
sha: 
doc_id: 299699
cord_uid: 9uiv3n41

• Critically-ill COVID-19 patients with New Delhi Metallo-beta-lactamase producing Enterobacterales infections at our medical center had poor outcomes, including death in 4 of 5 cases; • Multiple insults contributed to the occurrence of co-infection in these patients, including prolonged hospitalization, intubation, invasive devices, extensive antibiotic use, immunosuppressive therapy and environmental factors; • There are few antibiotic options for treatment of infections with New Delhi Metallo-beta-lactamase producing Enterobacterales, contributing to poor outcomes; • Hospitals and public health authorities should be vigilant for extensively drug resistant bacterial co-infections in patients hospitalized with COVID-19.

Four of five patients succumbed to septic shock due to advanced COVID-19, polymicrobial infection, or both. Average length of hospitalization prior to death (n = 4) or discharge (n = 1) was 29.4 days.

Since 2012, NDM has been increasingly reported in US patients without international healthcare exposure (4). Healthcare-associated NDM-1 E. cloacae outbreaks characterized using whole genome sequencing demonstrated persistence of resistant strains for over two years, despite rigorous control measures (5) . Screening for colonization without specific epidemiologic risk factors is not universally performed (4).

Antimicrobial stewardship programs have a crucial role in limiting excess antibiotic use and providing expertise on extensively drug-resistant infections, however, treatment of class B MBLs remains challenging. New β-lactamase inhibitors only have activity against Ambler class A and D serine β-lactamases but not MBLs (6) . The presence of co-existing resistance mechanisms leave few therapeutic options. Polymyxins are limited by unfavorable side effects, emerging resistance and poor outcomes (7) . Tigecycline has limited in-vivo efficacy for severe infections and benefits of higher dosing remains unclear (7) . Certain NDM-producing isolates also possess 16S rRNA methylases, rendering aminoglycosides ineffective (4) The combination of aztreonam and ceftazidime-avibactam has theoretic activity against NDMproducing Enterobacterales. Aztreonam is not hydrolyzed by MBLs but its use is limited by coexisting serine β-lactamases (7) Avibactam has no activity against MBLs but may protect In conclusion, hospitals should conduct close monitoring for excess antibiotic use and digression from infection prevention bundles during the COVID-19 pandemic to prevent emergence of extensively drug resistant infections with limited antibiotic options. Intensified commitment to new drug development is urgently needed as part of pandemic planning. Coordinated hospital and public health antimicrobial resistance surveillance will be required for many years post COVID-19.

Funding: No funding source 

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