Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.

BACKGROUND: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. METHODS: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. RESULTS: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 µg/mL in the HD group, which was higher than in the SD group (0,21 µg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. CONCLUSIONS: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU.

Purpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU. Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP. Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237). Conclusions: Blakpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.

Physicians' knowledge, attitude, and prescribing behavior regarding stress ulcer prophylaxis in China: a multi-center study.

BACKGROUND: Perioperative patients are at risk of developing stress ulcers (SU), which can cause clinically important bleeding. Stress ulcer prophylaxis (SUP) is widely applied to the patients in Intensive care unit (ICU) as well as the general ward, so it may lead to overmedication. However, there have been no surveys regarding SUP knowledge or prescribing habits. OBJECTIVE: Our study assessed the knowledge, attitudes, and prescribing behavior of the surgeons toward perioperative patients regarding SUP and determined factors associated with low knowledge and high level of prescribing behaviors. METHODS: We performed a cross-sectional survey using questionnaires, randomly sampling 1266 surgeons on their current SUP practices. RESULTS: Proton pump inhibitors for SUP were used the most (94%); 43% used lansoprazole. Guideline awareness was inconsistent; the most familiar guideline was the National Medical Journal of China, and 46% were unaware of any guidelines. The predictors of low knowledge score regarding SUP in multivariable analysis were the hospital grade (p = 0.000), the type of hospital (p = 0.044), attendance at continuing education programs (p = 0.037), the awareness of clinical practice guidelines (CPGs) for SUP (p = 0.000). Twenty-one percent of physicians were high prescribers. High prescribing behavior was associated with hospital grade(p = 0.000), education level(p = 0.010) and attendance at continuing education programs (p = 0.000). CONCLUSION: We found that most surgeons used SUP, primarily proton pump inhibitors. However, surgeons knew little about the SUP guidelines, which may lead to insufficient SUP knowledge and overmedication. In addition, hospital grade, the type of hospital and attendance at continuing education programs may also affect the low knowledge of SUP. Hospital grade, education level and attendance at continuing education programs may affect high prescribing behavior.

High-Dose Tigecycline in Elderly Patients with Pneumonia Due to Multidrug-Resistant Acinetobacter baumannii in Intensive Care Unit.

PURPOSE: The association between clinical and microbiological outcomes and high-dose tigecycline (TGC) was assessed in elderly (≥60 years old) patients with hospital-acquired and ventilator-associated pneumonia due to multidrug-resistant Acinetobacter baumannii(A. baumannii). This study also assessed tigecycline combination with different antibiotics and its influence on the outcome. PATIENTS AND METHODS: An observational retrospective cohort study was conducted. Patients over 60 years old were treated with standard-dose (SD) TGC (100-mg intravenous TGC initially, followed by 50-mg doses administered intravenously twice daily) and high-dose (HD) TGC (200-mg intravenous TGC initially, followed by 100-mg doses administered intravenously twice daily) for a microbially confirmed infection. The outcome was 30-day crude mortality, co-administered antimicrobial agent and the microbial eradication percentage in both groups. RESULTS: A total of 48 multidrug-resistant A. baumannii respiratory patients were identified. Tigecycline was administered to 85% of ventilation-associated pneumonia (VAP) patients (28/33) in the SD group and 80% of VAP patients (12/15) in the HD group. Combined therapy was the major treatment option in both groups, accounting for 85% and 87%, respectively. Median treatment duration in both groups was 7.36 vs 8.6 days, respectively. Survival days were 13.61 vs 12.4 days (P=0.357), respectively. The 30-day crude mortality was 39.4% (13/33) for the SD group and 14% (2/15) for the HD group (P=0.098). The microbial eradication rate of respiratory specimens in the SD group was higher than that in the HD group (P=0.02). The variables associated with 30-day crude mortality were chronic obstructive pulmonary disease (hazard ratio [HR] 11.63, 95% CI 1.094-123.058; P=0.042), tigecycline treatment duration (HR 0.690, 95% CI 0.515-0.926; P=0.013), and surgery before infection (HR 79.276, 95% CI 6.983-899.979; P=0.000). High-dose tigecycline was not associated with 30-day crude mortality (adjusted HR 0.329, 95% CI 0.074-1.460; P=0.145). Combined antibiotics was also not different between the two groups. CONCLUSIONS: High-dose tigecycline was not associated with 30-day crude mortality in elderly patients with pneumonia due to multidrug-resistant A. baumannii, although the microbial eradication rate was high.

Associations Between Potentially Inappropriate Medications and Adverse Health Outcomes in the Elderly: A Systematic Review and Meta-analysis.

Background: Adverse drug outcomes in the elderly have led to the development of lists of potentially inappropriate medications (PIMs), such as the Beers criteria, and these PIMs have been studied widely; however, it is still unclear whether PIM use is predictive of adverse outcomes in older people. Objective: To qualitatively examine the associations between exposure to PIMs from the general Beers criteria and the Screening Tool of Older Persons' Prescriptions list and adverse outcomes, such as adverse drug reactions (ADRs)/adverse drug events (ADEs), hospitalization, and mortality. Methods: Specified databases were searched from inception to February 1, 2018. Two reviewers independently selected studies that met the inclusion criteria, assessed study quality, and extracted data. Data were pooled using Stata 12.0. The outcomes were ADRs/ADEs, hospitalization, and mortality. Results: A total of 33 studies met the inclusion criteria. The combined analysis revealed a statistically significant association between ADRs/hospitalizations and PIMs (odds ratio [OR] = 1.44, 95% CI = 1.33-1.56; OR = 1.27, 95% CI = 1.20-1.35), but no statistically significant association was found between mortality and PIMs (OR = 1.04; 95% CI = 0.75-1.45). It is interesting to note that the results changed when different continents/criteria were used for the analysis. Compared with the elderly individuals exposed to 1 PIM, the risk of adverse health outcomes was much higher for those who took ≥2 PIMs. Conclusion and Relevance: We recommend that clinicians avoid prescribing PIMs for older adults whenever feasible. In addition, the observed associations should be generalized to other countries with different PIM criteria with caution.

Fabrication of PP hollow fiber membrane via TIPS using environmentally friendly diluents and its CO2 degassing performance.

CO2 removal is an essential water purification process in many fields, such as petrochemical production and thermal power generation. It is challenging to remove low concentrations of CO2 from RO effluent water. The core component of the membrane degassing technique is a high-performance hydrophobic microporous membrane. Polypropylene (PP) membranes were prepared with environmentally friendly binary diluents via thermally induced phase separation. Firstly, the effects of PP concentration on the phase diagram, flat sheet membrane structure and mechanical properties were studied to optimize the PP content for a hollow fiber membrane (HFM). The PP HFM showed a sponge-like cross-sectional structure without any dense skin layer, a large loading force and breaking elongation, and a narrow pore size distribution with a mean pore size of 0.16 µm. The as-fabricated PP HFM module was applied for CO2 removal from RO effluent water from a petrochemical plant. A higher water temperature and vacuum degree facilitated CO2 removal. Increasing the effective membrane length enhanced degassing efficiency. Increasing the water flow rate increased CO2 degassing flux, but simultaneously decreased degassing efficiency. When the water flow rate increased from 20 mL min-1 to 63 mL min-1, although the effective membrane length increased from 3 m to 4.8 m for the best degassing efficiency of 88%, the amount of treated water increased by 3.15 times. The declined CO2 concentration in the outlet water was 1.6 mg L-1.

Efficacy and safety of tigecycline monotherapy versus combination therapy for the treatment of hospital-acquired pneumonia (HAP): a meta-analysis of cohort studies.

The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.

Allergic shock and death associated with protamine administration in a diabetic patient.

BACKGROUND: Insulin is used to treat patients with both type 1 and type 2 diabetes mellitus. Allergic reactions to insulin might be triggered by insulin itself or inactive ingredients in the insulin formulation, including proteins such as protamine in neutral protamine Hagedorn (NPH) insulin. The use of highly purified animal insulin and human recombinant insulin has reduced the incidence of anaphylactic reactions to insulin from ~30% to <1%. OBJECTIVE: We report a case of fatal allergic shock after the administration of protamine in a patient with a history of allergy to fish and a protamine-containing insulin. CASE SUMMARY: A 72-year-old Chinese male patient (height, 175 cm; weight, 80 kg) with a history of diabetes and progressive limb weakness was diagnosed with spinal vascular malformations after admission to the Xuan Wu Hospital of Capital Medical University, Beijing, People's Republic of China. He underwent epidural spinal cord arteriovenous fistula embolization with a liquid embolic agent (ethylene vinyl alcohol copolymer) after spinal cord angiography. During the operation, heparin was infused every hour with 6250, 2500, 2500, and 1250 IU, respectively. The last dose of heparin was administered ~10 minutes before the operation was completed. This was followed by the administration of protamine to neutralize the remaining heparin in the patient's body. Blurry vision and dizziness 5 minutes after protamine administration were followed by pruritus and hives over his neck and face. Oxygen was administered and 10 mg of dexamethasone with 2 mg of epinephrine was injected. The patient's heart rate dropped, his blood pressure decreased, and his arterial oxygen saturation (SaO2) declined progressively. About 10 minutes after the administration of protamine sulfate, the patient developed bradycardic arrest. Cardiopulmonary resuscitation efforts were undertaken and the patient was administered epinephrine 2 mg IV, atropine 0.5 mg IV, and subsequently, intravenous dopamine (50 mg/h). Ten minutes later, the patient's heart rate gradually increased, but blood pressure fluctuated, and SaO2 ranged from 90% to 100%. Despite the initial response, the patient lost consciousness and heart rate declined progressively within 5 hours. Vasoactive agents including dopamine, norepinephrine, and adrenaline were administered. After all these measures proved ineffectual, the patient died. It was later determined that the patient had a history of allergic reactions to fish as well as to a premixed insulin that contained soluble human insulin 30% and low-protein intensive insulin zinc 70% (NPH). The Naranjo adverse drug reaction probability scale score for the association of protamine with the allergic reaction was 4, suggesting a possible relationship. CONCLUSION: This case report highlights a preventable fatal allergic reaction possibly associated with protamine administration in a patient with a history of allergy to a protamine-containing insulin.