Polymyxin use associated with respiratory arrest.
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ABSTRACT:
SUBMITTER: Wunsch H
PROVIDER: S-EPMC3662206 | biostudies-other | 2012 Feb
REPOSITORIES: biostudies-other
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Project description:Regimens containing topical polymyxin appear highly effective at preventing ventilator-associated pneumonia (VAP) overall and, more so, VAP caused by Gram-negative bacteria. However, Stoutenbeek's postulates that VAP incidences within studies of topical antibiotics depend on the context of whether the component (control and intervention) groups of each study were concurrent versus nonconcurrent remain untested. The literature was searched for concurrent control (CC) versus nonconcurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported incidences of Pseudomonas-associated ventilator-associated pneumonia (PsVAP). Studies of various interventions other than topical polymyxin (nonpolymyxin studies) served to provide additional points of reference. The PsVAP incidences within the component groups of all studies were benchmarked against groups from observational studies. This was undertaken by meta-regression using generalized estimating equation methods. Dot plots, caterpillar plots, and funnel plots enable visual benchmarking. The PsVAP benchmark (and 95% confidence interval [CI]) derived from 102 observational groups is 4.6% (4.0 to 5.3%). In contrast, the mean PsVAP within NCC polymyxin intervention groups (1.6%; CI, 1.0 to 4.5%) is lower than that of all other component group categories. The mean PsVAP within CC polymyxin control groups (9.9%; CI, 7.6 to 12.8%) is higher than that of all other component group categories. The PsVAP incidences of control and intervention groups of studies of respiratory tract applications of polymyxin are dependent on whether the groups were within a concurrent versus nonconcurrent study. Stoutenbeek's concurrency postulates are validated.
| S-EPMC6105782 | biostudies-literature
Project description:Polymyxins (polymyxin B and colistin) are older bactericidal antibiotics that are increasingly used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, dosing and clinical use of these drugs vary widely. This survey was undertaken to reveal how polymyxins are used worldwide. Data were collected through a structured online questionnaire consisting of 24 questions regarding colistin usage patterns and indications as well as colistin dosage for adult patients. The questionnaire was disseminated in 2011 to relevant experts worldwide and was completed by 284 respondents from 56 different countries. Respondents from 11/56 countries (20%) had no access to colistin; 58/284 respondents (20.4%) reported that in 2010 they experienced that colistin was not available when needed. Formulations of polymyxins used were reported as: colistimethate sodium (48.6%); colistin sulfate (14.1%); both (1.4%); polymyxin B (1.4%); and unknown. Intravenous formulations were used by 84.2%, aerosolised or nebulised colistin by 44.4% and oral colistin for selective gut decontamination by 12.7%. Common indications for intravenous colistin were ventilator-associated pneumonia, sepsis and catheter-related infections with MDR Gram-negative bacteria. Only 21.2% of respondents used a colistin-loading dose, mainly in Europe and North America. This survey reveals that the majority of respondents use colistin and a few use polymyxin B. The survey results show that colistin is commonly underdosed. Clear guidance is needed on indications, dosing and antibiotic combinations to improve clinical outcomes and delay the emergence of resistance. Colistin should be considered a last-resort drug and its use should be controlled. International guidelines are urgently needed.
| S-EPMC3991322 | biostudies-literature
Project description:IntroductionElectronic cigarettes (ECIGs) expose users to an aerosol containing chemicals, which could affect the respiratory system negatively. This study examined negative respiratory symptoms associated with ECIG use.MethodsIn 2019, adult current ECIG users from 24 US states who reported experiencing negative respiratory symptoms from ECIG use (n = 49; 44.9% women; mean age = 35.2, SD = 11.5) completed an online survey and brainstormed statements that completed the prompt: "A specific negative effect or symptom related to my breathing, nose, mouth, throat, or lungs that I have experienced from vaping/using my e-cigarette is..." Participants sorted the final list of 56 statements into groups of similar content and rated statements on how true they were for them. Multidimensional scaling analysis identified thematic clusters.ResultsEight ECIG use respiratory symptom clusters identified in analysis included Mucus and Congestion, Fatigue, Throat Symptoms, Breathing Problems, Mouth Symptoms, Chest Symptoms, Illness Symptoms, and Nose and Sinus Symptoms. Highly rated (ie, most common) symptoms included dry throat or mouth, fatigue during physical activity, coughing, shortness of breath, excessive phlegm, and bad taste in mouth. Mean cluster ratings did not differ based on lifetime cigarette smoking status (100 lifetime cigarettes smoked), but current cigarette smokers (ie, dual users) rated the Fatigue, Breathing Problems, Mucus and Congestion, and Nose and Sinus Symptoms clusters higher than noncurrent cigarette smokers.ConclusionsParticipant-identified respiratory symptoms perceived to be ECIG related, many similar to cigarette smoking symptoms. Future research should assess if these symptoms are associated with other negative health outcomes.ImplicationsECIG use exposes users to chemicals that may have negative health impacts on the respiratory system. Limited research has examined the broad range of negative respiratory symptoms associated with e-cigarette use. This study identified that ECIG-cigarette users perceive their ECIG use to be associated with negative respiratory symptoms. Many e-cigarette user-reported negative respiratory symptoms are similar to those associated with cigarette smoking, though some appear unique to e-cigarette use. Future research should continue to monitor respiratory symptoms reported by ECIG users and whether these are associated with health outcomes over time.
| S-EPMC7737476 | biostudies-literature
Project description:BACKGROUND:Cannabis use is a potential risk factor for respiratory disease but its role apart from tobacco use is unclear. We evaluated the association between regular cannabis use, with and without tobacco co-use, and onset of asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. METHODS:Analysis of a limited data set obtained through IBM Watson Health Explorys, an electronic-health-record-integration platform. Matched controls using Mahalanobis distance within propensity score calipers were defined for: 1) cannabis-using patients (n?=?8932); and subgroups of cannabis-using patients: 2) with an encounter diagnosis for tobacco use disorder (TUD; n?=?4678); and 3) without a TUD diagnosis (non-TUD; n?=?4254). Patients had at least: one recorded blood pressure measurement and one blood chemistry lab result in the MetroHealth System (Cleveland, Ohio). Cannabis-using patients had an encounter diagnosis of cannabis abuse/dependence and/or ?2 cannabis-positive urine drug screens (UDSs). Control patients, not having cannabis-related diagnoses or cannabis-positive UDSs, were matched to the cannabis-using patients on demographics, residential zip code median income, body mass index, and, for the total sample, TUD-status. RESULTS:Regular cannabis use was significantly associated with greater risk for asthma (odds ratio (OR)?=?1.44; adjusted odds ratio (aOR)?=?1.50; OR?=?1.32), COPD (OR?=?1.56; aOR?=?1.44; OR?=?2.17), and pneumonia (OR?=?1.80; OR?=?1.84; OR?=?2.13) in the total sample and TUD and non-TUD subgroups, respectively. TUD-patients had the greatest prevalence of respiratory disease, regardless of cannabis-use indication. CONCLUSIONS:Regular cannabis use is associated with significantly greater risk of respiratory disease regardless of TUD status. Future research to understand the impact of cannabis use on respiratory health is warranted.
| S-EPMC6878136 | biostudies-literature
Project description:We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were significant differences in terms of antibiotic susceptibility and genetic determinants of resistance in A. baumannii isolates that had developed polymyxin B resistance in vivo compared to isolates that had developed polymyxin B resistance in vitro.
| S-EPMC4649193 | biostudies-literature
Project description:Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD), and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were examined in neutropenic infected mice, and the data were analyzed by a population PK model. Dose fractionation study was performed for total daily doses between 2.06 and 24.8 mg base/kg of weight against Pseudomonas aeruginosa ATCC 27853, PAO1, and FADDI-PA022 (MIC of 1 mg/liter for all three strains). Histopathological examination of the lung was undertaken at 24 h posttreatment in both healthy and neutropenic infected mice. A two-compartment PK model was required for both epithelial lining fluid (ELF) and plasma drug exposure. The model consisted of central and peripheral compartments and was described by bidirectional first-order distribution clearance. The ratio of the area under the curve to the MIC (AUC/MIC) was the most predictive PK/PD index to describe the antimicrobial efficacy of aerosolized polymyxin B in treating lung infections in mice (R2 of 0.70 to 0.88 for ELF and 0.70 to 0.87 for plasma). The AUC/MIC targets associated with bacteriostasis against the three P. aeruginosa strains were 1,326 to 1,506 in ELF and 3.14 to 4.03 in plasma. Histopathological results showed that polymyxin B aerosols significantly reduced lung inflammation and preserved lung epithelial integrity. This study highlights the advantageous PK/PD characteristics of pulmonary delivery of polymyxin B over intravenous administration in achieving high drug exposure in ELF.
| S-EPMC5527630 | biostudies-literature
Project description:Polymyxin E belongs to cationic polypeptide antibiotic bearing four types of direct precursor amino acids including L-2,4-diaminobutyric acid (L-Dab), L-Leu, D-Leu, and L-Thr. The objective of this study is to evaluate the effect of addition of precursor amino acids during fermentation on polymyxin E biosynthesis in Paenibacillus polymyxa. The results showed that, after 35?h fermentation, addition of direct precursor amino acids to certain concentration significantly inhibited polymyxin E production and affected the expression of genes involved in its biosynthesis. L-Dab repressed the expression of polymyxin synthetase genes pmxA and pmxE, as well as 2,4-diaminobutyrate aminotransferase gene ectB; both L-Leu and D-Leu repressed the pmxA expression. In addition, L-Thr affected the expression of not only pmxA, but also regulatory genes spo0A and abrB. As L-Dab precursor, L-Asp repressed the expression of ectB, pmxA, and pmxE. Moreover, it affected the expression of spo0A and abrB. In contrast, L-Phe, a nonprecursor amino acid, had no obvious effect on polymyxin E biosynthesis and those biosynthesis-related genes expression. Taken together, our data demonstrated that addition of precursor amino acids during fermentation will inhibit polymyxin E production probably by affecting the expression of its biosynthesis-related genes.
| S-EPMC4454717 | biostudies-literature
Project description:Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive, and thus, novel techniques, including human microphysiological systems, or “organs on chips,” are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; yet clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.2 ×10–16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)–like 2 pathway despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and NAB741 and reveal cholesterol biosynthesis as the novel (to our knowledge) pathway for PMB- induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule.
2019-01-23 | GSE123264 | GEO
Project description:In order to provide an idea dose of polymyxin B in Chinese patients with renal impairment, the present study collected the clinical data of all patients with renal impairment who received polymyxin B therapy in the intensive care unit (ICU) of The First Affiliated Hospital of Bengbu Medical College (Bengbu, China). The clinical data of six patients treated in the ICU between February 2018 and May 2019 were retrospectively analyzed. All patients had renal impairment and were treated with polymyxin B combination therapy. The patients in the current study received polymyxin B and carbapenem, or polymyxin, carbapenem, cefoperazon and sulbactam, or polymyxin B, carbapenems and aminoglycoside treatment. One patient discontinued treatment. The other five patients received polymyxin B at a dosage of 50 mg every 12 h (100 mg/day) through an intravenous drip. During treatment, four of the five patients had deteriorating renal function to varying degrees, and continuous renal replacement therapy (CRRT) was initiated. Polymyxin B was discontinued in all patients when the infection was controlled. After treatment, four of five patients showed improvement in renal function, and had normal kidney function at the 1-month follow-up evaluation, whereas one patient had chronic renal disease. During hospitalization, one patient experienced neurotoxicity, showing decreased limb muscle strength and cognitive impairment, which might have been caused by polymyxin B, according to the Naranjo adverse drug reactions probability scale (also known as the Naranjo algorithm) score. The present report demonstrated that the administration of 100 mg daily dosage of polymyxin B to the five patients weighing between 50 and 75 kg, could control pulmonary infection during the course of treatment of Chinese patients with renal impairment, however, further research is needed to verify this result. Risk factors for nephrotoxicity and neurotoxicity need to be fully assessed before initiating polymyxin B therapy in patients with renal impairment.
| S-EPMC7506961 | biostudies-literature
Project description:Response of three strains, K56-2, RSF34, and RSF34 4000B to polymyxin B and baseline changes between the strains
2011-06-01 | E-MTAB-720 | biostudies-arrayexpress