Mary Wilson
Well-known member
Published: February 09, 2023
DOI: https://doi.org/10.1016/S2666-5247(22)00329-9
Jinnethe Reyes, PhD, Lauren Komarow, MS, Liang Chen, PhD, Lizhao Ge, MAS, Blake M Hanson, PhD,
Eric Cober, MD et al. Show all authors
Summary
Background
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical signi cance of carbapenemases are unclear. The aim of this study was to de ne characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.
Methods
We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality.
Findings
We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality di ered by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; di erence 9%, 95% CI 3–16) and adjusted (di erence 7%, 95% CI 1–14) analyses.
Interpretation
The emergence of di erent carbapenemases among CRPA isolates in di erent geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms.
https://www.thelancet.com/action/showPdf?pii=S2666-5247(22)00329-9
DOI: https://doi.org/10.1016/S2666-5247(22)00329-9
Jinnethe Reyes, PhD, Lauren Komarow, MS, Liang Chen, PhD, Lizhao Ge, MAS, Blake M Hanson, PhD,
Eric Cober, MD et al. Show all authors
Summary
Background
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical signi cance of carbapenemases are unclear. The aim of this study was to de ne characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.
Methods
We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality.
Findings
We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality di ered by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; di erence 9%, 95% CI 3–16) and adjusted (di erence 7%, 95% CI 1–14) analyses.
Interpretation
The emergence of di erent carbapenemases among CRPA isolates in di erent geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms.
https://www.thelancet.com/action/showPdf?pii=S2666-5247(22)00329-9