RESUMEN
BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define 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 differed 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; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.
Asunto(s)
Antibacterianos , Infecciones por Pseudomonas , Estados Unidos , Humanos , Antibacterianos/uso terapéutico , Pseudomonas aeruginosa/genética , Estudios Prospectivos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Carbapenémicos/uso terapéuticoRESUMEN
Orofacial clefts (OFCs) have multifactorial etiologies. Prenatal exposure to heavy metals can induce OFCs in animal models, but evidence from studies of human subjects is scarce. We examined whether concentrations of mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) in placental tissues are associated with risk for OFCs in offspring. This population-based case-control study included 103 newborns affected by OFCs with available placental tissues and 206 controls randomly selected from 509 non-malformed newborns with available placenta samples, recruited in five rural counties in northern China. Sociodemographic information was collected using a structured questionnaire in face-to-face interviews. The concentrations of Hg, Cd, Pb, and As in placental tissues were analyzed using an inductively coupled plasma-mass spectrometry in helium mode. The median concentrations of Hg (7.4â¯ng/g), Cd (57.1â¯ng/g), and Pb (96.1â¯ng/g) were all statistically significantly higher in OFC cases than in controls (Hg 5.5â¯ng/g, Cd 38.6â¯ng/g, and Pb 67.9â¯ng/g, respectively); no differences were observed between the two groups in median concentrations of As. Concentrations above the median for all subjects were associated with a 2.33-fold (95% confidence interval [CI] 1.33-2.09) increased OFC risk for Cd and a 3.08-fold (95% CI 1.74-5.47) increased risk for Pb. The risk for OFCs increased with concentration tertiles, with an adjusted odds ratio of 3.06 (95% CI 1.36-6.88) for the second tertile and 8.18 (95% CI 6.64-18.37) for the highest tertile of Cd, and 3.88 (95% CI 1.78-8.42) for the second tertile and 5.17 (95% CI 2.37-11.29) for the highest tertile of Pb. The association between Hg concentration and OFC risk was borderline nonsignificant after adjusting for confounding factors. Prenatal exposure to Cd and Pb, as reflected by their concentrations in placental tissues, is associated with an increased risk for neonatal OFCs.