Risk factors and clinical significance of bacteremia caused by Pseudomonas aeruginosa resistant only to carbapenems

Background/purposeCarbapenem-resistant Pseudomonas aeruginosa infections have been a challenge and issue in hospital settings. However, the clinical impact of P. aeruginosa blood isolates resistant only to carbapenems has never been discussed previously.MethodsTo assess the risk factors and clinical significance of bacteremia caused by carbapenem resistance only P. aeruginosa (CROPA), a 6-year retrospective case–control study was conducted. The CROPA strains were defined as isolates susceptible to ciprofloxacin, antipseudomonal penicillins and cephalosporins, and aminoglycosides but resistant to one antipseudomonal carbapenem (imipenem or meropenem) or both. The controls were selected among patients with bacteremia due to P. aeruginosa susceptible to all above classes of antipseudomonal antibiotics, which was defined as all-susceptible P. aeruginosa.ResultsTwenty-five patients had at least one blood culture positive for CROPA, and 50 controls had all-susceptible P. aeruginosa bacteremia. CROPA bacteremia had a high 30-day mortality rate (72.0%), as compared to 26.0% for the controls (p < 0.001). Through multivariate analysis, carbapenem exposure was the only risk factor for developing CROPA bacteremia (p = 0.002). A comparison between the surviving and deceased patients with CROPA bacteremia showed that nine (50%) of those who died, but none of the survivors, received carbapenems as the initial empirical therapy (p = 0.027).ConclusionCarbapenem exposure was associated with emergence of CROPA infections. Repeated carbapenem use in such patients might increase rates of inappropriate initial empirical treatment and mortality. Prudent carbapenem use is important to reduce the emergence of CROPA

Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation

BACKGROUND: Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. OBJECTIVES: The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. METHODS: Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. RESULTS: At the cutoff values of eGFR of 50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as “on label” based on MDRD or CKD-EPI, only those whose dosages were “truly on label” based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin. CONCLUSIONS: The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages

Pseudomonas aeruginosa sepsis with ecthyma gangrenosum and pseudomembranous pharyngolaryngitis in a 5-month-old boy

Pseudomonas aeruginosa infection that induced pseudomembranous laryngopharyngitis and ecthyma gangrenosum simultaneously in a healthy infant is rare. We reported on a previously healthy 5-month-old boy with initial presentation of fever and diarrhea followed by stridor and progressive respiratory distress. P. aeruginosa sepsis was suspected because ecthyma gangrenosum over the right leg was found at the emergency department, and the diagnosis was confirmed by the blood culture. Fiberscope revealed bacterial pharyngolaryngitis without involvement of the trachea. Because of early recognition and adequate treatment, including antimicrobial therapy, noninvasive ventilation, incision, and drainage, he recovered completely without any complications

Lung Epithelial TRPA1 Mediates Lipopolysaccharide-Induced Lung Inflammation in Bronchial Epithelial Cells and Mice

Toll-like receptor (TLR) 4 was originally thought to be the sole pattern recognition receptor for lipopolysaccharide (LPS). Transient receptor potential ankyrin 1 (TRPA1), a Ca2+-permeant channel, has been suggested as a non-TLR receptor membrane-bound sensor of LPS. We recently reported that TRPA1 is expressed in lung epithelial cells (LECs) and mediates lung inflammation induced by cigarette smoke. However, the role of TRPA1 in LPS-induced lung inflammation has not been conclusively defined, and its underlying cellular mechanisms remain unclear. In this study, our in vitro results showed that LPS sequentially produced a cascade of events, including the elevation of intracellular Ca2+, the activation of NADPH oxidase, increase in intracellular reactive oxygen species (ROS), the activation of mitogen-activated protein kinase (MAPK)/nuclear factor-kB (NF-κB) signaling, and the induction of IL-8. The increase in intracellular Ca2+ was inhibited by HC030031 (a TRPA1 antagonist) but was unaffected by TAK-242 (a TLR-4 inhibitor). The activation of NADPH oxidase was prevented by its inhibitor apocynin, EGTA (an extracellular Ca2+ chelator), and HC030031. The increase in intracellular ROS was attenuated by apocynin, N-acetyl-cysteine (NAC, a ROS scavenger), EGTA, and HC030031. The activation of the MAPK/NF-κB signaling was halted by NAC, EGTA, and HC030031. IL-8 induction was suppressed by HC030031 and TRPA1 siRNA, and further reduced by the combination of HC030031 and TAK-242. Our in vivo studies showed that trpa1–/– mice exhibited a reduced level of LPS-induced lung inflammation compared with wild-type mice as evidenced by the alleviations of increases in vascular permeability, inflammatory cell infiltration, inflammatory cytokine levels, oxidative stress, and MAPK signaling activation. Thus, in LECs, LPS may activate TRPA1 resulting in an increase in Ca2+ influx. The increased intracellular Ca2+ leads to NADPH oxidase activation, which causes an increase in intracellular ROS. The intracellular ROS activates the MAPK/NF-κB signaling resulting in IL-8 induction. This mechanism may possibly be at work to induce lung inflammation in mice

Present-Day Lake Level Variation from Envisat Altimetry over the Northeastern Qinghai-Tibetan Plateau: Links with Precipitation and Temperature

Lakes in permafrost regions are highly sensitive to changes in air temperature, snowmelt, and soil frost. In particular, the Qinghai-Tibetan Plateau (QTP) is one of the most sensitive regions in the world influenced by global climate change. In this study, we use retracked Enivsat radar altimeter measurements to generate water level change time series over Lake Qinghai and Lake Ngoring in the northeastern QTP and examine their relationships with precipitation and temperature changes. The response of water levels in Lake Qinghai and Lake Ngoring is positive with regards to precipitation amount. There is a negative relationship between water level and temperature change. These findings further the idea that the arid and high-elevation lakes in the northeastern QTP are highly sensitive to climate variations. Water level increases in Lake Qinghai in winter may indicate inputs of subsurface water associated with freeze-thaw cycles in the seasonally frozen ground and the active layer

Outcomes and characteristics of ertapenem-nonsusceptible Klebsiella pneumoniae bacteremia at a university hospital in Northern Taiwan: A matched case-control study

Background and purposeCarbapenem-resistant Klebsiella pneumoniae is an emerging problem worldwide. The object of this study was to investigate the risk factors, characteristics and outcomes of ertapenem-nonsusceptible K pneumoniae (ENSKp) bacteremia.MethodsWe conducted a 1:2 ratio matched case-control study. The controls were randomly selected among patients with ertapenem-susceptible K pneumoniae (ESKp) bacteremia and were matched with ENSKp cases for bacteremia.ResultsSeventy-five patients were included in this study (25 cases and 50 controls). Bivariate analysis showed that prior exposure to either β-Lactam/β-Lactam-lactamase inhibitors (p = 0.008) or 4th generation cephalosporins (p < 0.001), chronic obstructive pulmonary disease (COPD) (p = 0.001), acute renal failure (p = 0.021), chronic kidney disease without dialysis (p = 0.021), recent hospital stay (p = 0.016), intensive care unit stay (p = 0.002), mechanical ventilation (p = 0.003), central venous catheter placement (p = 0.016), Foley indwelling (p = 0.022), polymicrobial bacteremia (p = 0.003) and higher Pittsburgh bacteremia score (p < 0.001) were associated with ENSKp bacteremia. The multivariate analysis showed that prior exposure to 4th generation cephalosporins (odds ratio [OR], 28.05; 95% confidence interval [CI], 2.92–269.85; p = 0.004), COPD (OR, 21.38; 95% CI, 2.95–154.92; p = 0.002) and higher Pittsburgh bacteremia score (OR, 1.35; 95% CI, 1.10–1.66; p = 0.004) were independent factors for ENSKp bacteremia. ENSKp bacteremia had a higher 14-day mortality rate than ESKp bacteremia (44.0% vs. 22.0%; p = 0.049). The overall in-hospital mortality rates for these two groups were 60.0% and 40.0% respectively (p = 0.102).ConclusionENSKp bacteremia had a poor outcome and the risk factors were prior exposure of 4th generation cephalosporins, COPD and higher Pittsburgh bacteremia score. Antibiotic stewardship may be the solution for the preventive strategy

Differentiated cytoplasmic granule formation in quiescent and non-quiescent cells upon chronological aging

Stationary phase cultures represent a complicated cell population comprising at least two different cell types, quiescent (Q) and non-quiescent (NQ) cells. Q and NQ cells have different lifespans and cell physiologies. However, less is known about the organization of cytosolic protein structures in these two cell types. In this study, we examined Q and NQ cells for the formation of several stationary phase-prevalent granule structures including actin bodies, proteasome storage granules, stress granules, P-bodies, the compartment for unconventional protein secretion (CUPS), and Hsp42-associated stationary phase granules (Hsp42-SPGs). Most of these structures preferentially form in NQ cells, except for Hsp42-SPGs, which are enriched in Q cells. When nutrients are provided, NQ cells enter mitosis less efficiently than Q cells, likely due to the time requirement for reorganizing some granule structures. We observed that heat shock-induced misfolded proteins often colocalize to Hsp42-SPGs, and Q cells clear these protein aggregates more efficiently, suggesting that Hsp42-SPGs may play an important role in the stress resistance of Q cells. Finally, we show that the cell fate of NQ cells is largely irreversible even if they are allowed to reenter mitosis. Our results reveal that the formation of different granule structures may represent the early stage of cell type differentiation in yeast stationary phase cultures