Characteristics of community-Acquired carbapenem-resistant Enterobacterales

Background: Community-Acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat. Methods: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-Associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling. Results: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was the most common CRE species, of these 184/204 (90%) were carbapenemase producers (CPKP). The top three genetic markers in random forest models were kpi_SA15, fimE, and kpfC. Of these, kpi_SA15 (which encodes a chaperone/usher system) was positively associated (OR 3.14, 95% CI 1.13-8.87, P = 0.026), and kpfC negatively associated (OR 0.21, 95% CI 0.05-0.72, P = 0.015) with CA-CPKP. Conclusions: Ten percent of CDC-defined CRE were CA. The true proportion of CA-CRE in hospitalized patients is likely lower as patients may have had unrecorded prior healthcare exposure. The kpi_SA15 operon was associated with the CA phenotype

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

BACKGROUND: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. METHODS: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. RESULTS: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P \u3c .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P \u3c .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). CONCLUSIONS: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders

Epidemiología mundial y resultados clínicos de Pseudomonas aeruginosa resistente a carbapenemes y carbapenemasas asociadas (POP): un estudio prospectivo de cohortes

Antecedentes: La Pseudomonas aeruginosa resistente a los carbapenemes (CRPA) es una amenaza mundial, pero la distribución y la importancia clínica de las carbapenemasas no están claras. El objetivo de este estudio fue definir las características y los resultados de las infecciones por CRPA, así como la frecuencia global y el impacto clínico de las carbapenemasas albergadas por CRPA. Métodos: Llevamos a cabo un estudio de cohortes observacional y prospectivo de CRPA aislados de cultivos de torrente sanguíneo, respiratorio, orina o heridas de pacientes en 44 hospitales (10 países) entre el 1 de diciembre de 2018 y el 30 de noviembre de 2019. Los datos clínicos se extrajeron de los registros de salud y los aislados de CRPA se secuenciaron en todo el genoma. El resultado primario fue la mortalidad a 30 días a partir del día en que se recolectó el cultivo índice. Se compararon los resultados de los pacientes con infecciones por CRPA por tipo de infección y entre regiones geográficas y se realizó un análisis ponderado de probabilidad inversa para evaluar la asociación entre la producción de carbapenemasas y la mortalidad a 30 días. Resultados: Se incluyeron 972 pacientes (EE.UU. n=527, China n=171, América del Sur y Central n=127, Oriente Medio n=91, Australia y Singapur n=56), de los cuales 581 (60%) tenían infecciones por CRPA. La mortalidad a los 30 días difería según el tipo de infección (torrente sanguíneo 21 [30%] de 69, respiratoria 69 [19%] de 358, herida nueve [14%] de 66, orina seis [7%] de 88; p=0-0012) y la región geográfica (Oriente Medio 15 [29%] de 52, América del Sur y Central 20 [27%] de 73, EE.UU. 60 [19%] de 308, Australia y Singapur tres [11%] de 28, China siete [6%] de 120; p=0-0002). La prevalencia de genes carbapenemasa entre los aislados CRPA también varió según la región (América del Sur y Central 88 [69%] de 127, Australia y Singapur 32 [57%] de 56, China 54 [32%] de 171, Oriente Medio 27 [30%] de 91, EE.UU. diez [2%] de 527; p<0-0001). KPC-2 (n=103 [49%]) y VIM-2 (n=75 [36%]) fueron las carbapenemasas más comunes en 211 aislados productores de carbapenemasas. Después de excluir a los pacientes de EE.UU., porque pocos aislados de EE.UU. tenían carbapenemasas, los pacientes con infecciones por CRPA productoras de carbapenemasas tuvieron una mayor mortalidad a los 30 días que aquellos con infecciones por CRPA no productoras de carbapenemasas, tanto en los análisis no ajustados (26 [22%] de 120 frente a 19 [12%] de 153; diferencia 9%, IC 95% 3-16) como ajustados (diferencia 7%, IC 95% 1-14). Interpretación: La aparición de diferentes carbapenemasas entre los aislados de CRPA en diferentes regiones geográficas y el aumento de la mortalidad asociada a las infecciones por CRPA productores de carbapenemasas ponen de manifiesto los retos terapéuticos que plantean estos organismos. Financiación: Institutos Nacionales de Salud.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

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

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\u3c0·0001). 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

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

Background: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. Methods: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. Results: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P =. 079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P <. 001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P <. 001), and incident admission to a long-term care facility (22% vs 12%, P =. 045). Conclusions: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

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

Hypertonic Saline Use in Trauma Patients with Temporary Abdominal Closure

ABSTRACT Patients presenting with a variety of penetrating and blunt traumatic injuries require extensive perioperative management, resuscitation, and stabilization. This manuscript explores the indications of utilizing temporary abdominal closures, postoperative management of trauma patients with temporary abdominal closures, and how to best prevent potential complications. While some perioperative management is surgeon-specific, this manuscript highlights the advantages of standardizing the use of hypertonic saline for resuscitative fluid after damage control laparotomy for traumatic abdominal injuries requiring temporary abdominal closure

Expect the Unexpected! A Rare Case of Nocardia Bacteremia

Background: Nocardia species are partially acid fast, aerobic, gram-positive, branching filamentous bacteria that are found ubiquitously in the soil, decaying vegetable matter and aquatic environments. The Nocardia species most commonly associated with infections in humans are caused by asteroides (80-90%) followed by brasiliensis, farcinica and nova1. Nocardia spp. can cause serious pulmonary infections which are associated with frequent metastatic brain abscesses. Nocardia bacteremia is rarely reported and usually only seen in immunocompromised patients. We present a case of a central line associated Nocardia bloodstream infection in an immunocompetent patient. Case presentation: 53 year old Caucasian male with a history of a chronic small bowel stricture leading to oral intolerance and total parenteral nutrition (TPN) dependence initially presented with an intraabdominal abscess. The patient was immediately taken to the operative room for a laparotomy. Cultures from the operative room grew Enterococcus spp. and Salmonella spp. Patient was started on daptomycin, ceftriaxone and metronidazole to treat the infection. Blood cultures were also obtained and reported as Nocardia nova. CT chest and head and transesophageal echocardiogram did not reveal any evidence of disseminated Nocardiosis. The patient was then started on trimethoprim-sulfamethoxazole with plans to treat for three months followed by suppression therapy. The bacteremia source was thought to be from a 400 day old PICC due to the patient’s TPN dependence, which was removed. Conclusion: Nocardia infections in humans are uncommon, with a reported incidence in the United States of 500 to 1,000 new cases per year. Nocardia bacteremia is a rare event as a literature review from 1998 found only 36 cases of Nocardia bacteremia worldwide from the last 52 years3. Our patient had positive blood cultures with no evidence of disseminated Nocardiosis. Although, Nocardia species infections are mostly found in immunocompromised hosts, our patient’s long term PICC likely was the etiology for his bacteremia. This case illustrates the importance of monitoring central venous catheters as it can lead to central line-associated bloodstream opportunistic infections.https://scholarlycommons.henryford.com/merf2019caserpt/1033/thumbnail.jp

Epidemiology of multi drug resistant gram negative bacteria in Kathmandu, Nepal

Purpose: Multi drug resistant (MDR) bacterial infections are considered to be hospital-acquired in high income countries. Little data are available regarding the epidemiology of MDR bacteria in low and middle-income countries. Our study looked at the epidemiology of gram negative bacterial infections in Kathmandu, Nepal. Methods & Materials: Kathmandu Model Hospital is a 125 bed tertiary care hospital, in Kathmandu, Nepal. All patients hospitalized with MDR bacterial infections over a 12 month period were retrospectively evaluated. MDR bacteria included those with extended spectrum beta lactamase (ESBL), carbapenem (CRE) or colistin resistance. Age matched controls of patients with clinical infection but negative cultures were selected during the same time period. Water surveillance was performed to identify a potential source of environmental exposure. 55 vials were filled from various drinking water sources in Kathmandu; including bottled water, home reservoirs, and community taps. Water samples were analyzed by centrifugation and conventional culture techniques. Results: No significant differences in patient characteristics were noted between the groups (Table 1). Among the cases, 73% had E. coli, 15% had Acinetobacter sp (ACBC), and 12% had K. pneumoniae. The majority of infections in both groups were community acquired. 5 water samples from 4 locations were found to have ACBC. [Figure presented] Conclusion: Gram negative bacterial resistance is a prevalent concern in low and middle-income countries. Our study demonstrated gram negative bacteria in the drinking water in various locations throughout Kathmandu. This is a possible source of community acquired MDR bacterial infection