872 results on '"Cilastatin, Imipenem Drug Combination"'
Search Results
2. A Trial of Intravenous HRS-8427 in the Treatment of Adults With Complicate Urinary Tract Infection, Including Acute Pyelonephritis
- Published
- 2023
3. Patients Response to Early Switch To Oral:Osteomyelitis Study (PRESTO:Osteo)
- Author
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University of Louisville and Julio Ramirez, Professor of Medicine
- Published
- 2021
4. Efficacy and Safety of Colistin Based Antibiotic Therapy
- Author
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Ahmed Saeed Attia Mancy, Pharmacist
- Published
- 2021
5. Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) in Japanese Participants With Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection (MK-7655A-017)
- Published
- 2021
6. A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Participants With Impaired Renal Function (MK-7655-005)
- Published
- 2020
7. Evaluation of Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections
- Published
- 2020
8. Short Versus Extended Antibiotic Treatment With a Carbapenem for High-risk Febrile Neutropenia in Hematology Patients With FUO (SHORT)
- Author
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ZonMw: The Netherlands Organisation for Health Research and Development, FondsNutsOhra, and Nick de Jonge, MD
- Published
- 2019
9. Misdiagnosed Antibiotic-Induced Liver Injury: Unveiling Acute Hepatitis E in a 65-Year-Old Patient.
- Author
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Müller SL, Kaumanns A, Adam KM, Osthoff M, and Dräger S
- Subjects
- Humans, Male, Aged, Diagnostic Errors, Clindamycin adverse effects, Clindamycin therapeutic use, Cilastatin, Imipenem Drug Combination, Alanine Transaminase blood, Chemical and Drug Induced Liver Injury diagnosis, Chemical and Drug Induced Liver Injury etiology, Hepatitis E diagnosis, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents therapeutic use
- Abstract
BACKGROUND Common causes of severely elevated transaminases, especially alanine transaminase, due to liver diseases include drug-induced liver injury and acute viral hepatitis, especially hepatitis E, which can present similarly in clinical practice. Broad differential diagnostic workup in patients with elevated transaminases is required to not overlook the possibility of hepatitis E infection. CASE REPORT We report on a 65-year-old asymptomatic man who was referred to the Emergency Department from the rehabilitation center due to markedly elevated liver transaminases. Physical examination revealed no jaundice or abdominal pain. Laboratory findings included severely elevated aspartate transaminase, alanine transaminase, and bilirubin levels. He was previously treated with imipenem/cilastatin and clindamycin for a surgical site infection of his jaw after the removal of a squamous cell carcinoma 2 weeks earlier. An ultrasound of the liver was unremarkable. Drug-induced liver injury was suspected, and all potentially hepatotoxic drugs, including antibiotics, were stopped. Due to the rapid and marked increase in liver transaminases, further tests were performed, including testing for hepatitis E. Serum anti-hepatitis E virus immunoglobulin M, immunoglobulin G antibodies, and hepatitis E virus-ribonucleic acid-polymerase chain reaction turned positive, and the diagnosis of hepatitis E was confirmed. Supportive care was applied. Liver transaminases decreased spontaneously. CONCLUSIONS The diagnostic workup in patients with markedly elevated liver transaminases and suspected drug-induced liver injury should include the screening for hepatitis E. Making the correct diagnosis is crucial given the differing treatment approaches, the implications on further therapy, and the risk of contagion of hepatitis E.
- Published
- 2024
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10. Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013) (RESTORE-IMI 1)
- Published
- 2018
11. GSK2251052 in Complicated Urinary Tract Infection
- Published
- 2017
12. Complicated Skin and Skin Structure Infections
- Published
- 2017
13. Imipenem Prophylaxis in Patients With Acute Pancreatitis (IMPROWE)
- Author
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University of Rijeka and Goran Poropat, Postdoctoral Researcher
- Published
- 2017
14. A De-Escalating Strategy for Antibiotic Treatment of Pneumonia in The Medical Intensive Care Unit (0787B-092)
- Published
- 2017
15. Therapeutic drug monitoring of imipenem/cilastatin and meropenem in critically ill adult patients.
- Author
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You X, Dai Q, Hu J, Yu M, Wang X, Weng B, Cheng L, and Sun F
- Subjects
- Adult, Humans, Meropenem therapeutic use, Critical Illness, Drug Monitoring, Drug Combinations, Cilastatin, Imipenem Drug Combination, Imipenem therapeutic use, Cilastatin therapeutic use
- Abstract
Objectives: To investigate the factors influencing imipenem/cilastatin (IMI) and meropenem (MEM) concentrations in critically ill adult patients and the role of these concentrations in the clinical outcome., Methods: Plasma trough concentrations of IMI and MEM were detected by high-performance liquid chromatography. A target value of 100%-time above MIC was used for the drugs., Results: A total of 186 patients were included, with 87 receiving IMI and 99 receiving MEM. The percentages of patients reaching the target IMI and MEM concentrations were 44.8% and 38.4%, respectively. The proportions of patients infected with drug-resistant bacteria were 57.5% and 69.7% in the IMI group and MEM group, respectively. In the multivariate analysis, the risk factors for an IMI concentration that did not reach the target were infection with drug-resistant bacteria, and those for MEM were infection with drug-resistant bacteria, estimated glomerular filtration rate, and diabetes mellitus. A total of 47.1% of patients had good outcomes in the IMI cohort, and 38.1% of patients had good outcomes in the MEM cohort. The duration of mechanical ventilation and IMI concentration were associated with ICU stay in patients in the IMI cohort, while MEM concentration and severe pneumonia affected the clinical outcome of patients in the MEM cohort., Conclusion: Infection with drug-resistant bacteria is an important factor influencing whether IMI and MEM concentrations reach the target. Furthermore, IMI and MEM concentrations are associated with the clinical outcome, and elevated doses of IMI and MEM should be given to patients who are infected with drug-resistant bacteria., Competing Interests: Declaration of competing interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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16. Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.
- Author
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Pais GM, Marianski S, Valdez K, Melicor RP, Liu J, Rohani R, Chang J, Tong SYC, Davis JS, and Scheetz MH
- Subjects
- Rats, Male, Animals, Cilastatin, Imipenem Drug Combination, Clusterin, Rats, Sprague-Dawley, Anti-Bacterial Agents, Kidney, Biomarkers, Drug Combinations, Vancomycin pharmacology, Floxacillin
- Abstract
Background and Purpose: Vancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin-induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem-cilastatin on kidney injury when combined with vancomycin in our translational rat model., Experimental Approach: Male Sprague-Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem-cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule-1 (KIM-1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored., Key Results: Urinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM-1 increased on all days compared with vancomycin. In the vancomycin + imipenem-cilastatin group, urinary KIM-1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem-cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM-1., Conclusions and Implications: Vancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem-cilastatin in a translational rat model. The combination of vancomycin + imipenem-cilastatin was nephroprotective., (© 2023 British Pharmacological Society.)
- Published
- 2024
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17. Early outcomes of transcatheter arterial embolization using imipenem/cilastatin for plantar fasciitis refractory to conservative therapy.
- Author
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Gandhi R and Banker M
- Subjects
- Humans, Conservative Treatment, Treatment Outcome, Cilastatin, Imipenem Drug Combination, Fasciitis, Plantar surgery, Chronic Pain, Embolization, Therapeutic methods
- Abstract
Objective: The conservative therapy for chronic plantar fasciitis works for a few patients, while surgical options have drawbacks. Before considering surgical options, transcatheter arterial embolization may help patients with plantar fasciitis who are experiencing discomfort resistant to conservative treatment., Methods: We report evaluation data of 10 patients treated with transcatheter arterial embolization using imipenem/cilastatin as embolic agents to relieve chronic pain due to plantar fasciitis. All the patients were refractory to conservative therapy., Results: The technical success of the procedure was found to be 100%. Further, effective pain relief was observed as there was no pain relapse in 6 months, and patients did not require any other form of therapy., Conclusion: This report warrants further adequately designed randomized clinical studies for evaluating the efficacy of transcatheter arterial embolization in plantar fasciitis., Advances in Knowledge: Resorting to surgical option for chronic pain relief in plantar fasciitis might be reconsidered and replaced with arterial embolization. However, adequately designed long-term clinical studies are required to prove its long-term efficacy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)
- Published
- 2024
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18. Pharmacokinetics/Pharmacodynamics and tolerability of cefiderocol in the clinical setting
- Author
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J R, Azanza Perea and B, Sádaba Díaz de Rada
- Subjects
Adult ,Microbiology (medical) ,Pharmacology ,Iron ,Catechols ,Cilastatin, Imipenem Drug Combination ,Blood Proteins ,Meropenem ,General Medicine ,beta-Lactams ,beta-Lactamases ,Anti-Bacterial Agents ,Cephalosporins ,Albumins ,Humans - Abstract
Cefiderocol is a new cephalosporin with a catechol in its chemical structure faciliting its access to the interior of bacteria through iron channels. In addition, it is broadly stable to beta-lactamases. The pharmacokinetic profile is a beta-lactam one: no oral absorption, and with a wide distribution within the vascular space and the interstitial fluid of well vascularized tissues, reaching therapeutic concentrations in the alveolar lavage fluid and within the macrophage. The binding of cefiderocol to human plasma proteins, primarily albumin, is moderate (range 40-60%). The terminal elimination half-life in healthy adult subjects was 2 to 3 hours. Cefiderocol is mainly renally eliminated, so dose adjustments are recommended in subjects with moderate / severe renal impairment, in case of dialysis, and probably in patients with external clearance. Like other beta-lactams, the PK / PD parameter that has been shown to best correlate with efficacy is the efficacy time of unbound plasma concentrations (%fT>MIC), which must be close to 100% to achieve a bactericidal effect. This is possible with 2 g in a 3-hour infusion every 8 hours. In controlled trials appears to be well tolerated, similar to comparators: meropenem or imipenem-cilastatin. Cefiderocol has no apparent clinically significant effect on ECG parameters nor on plasma iron values.
- Published
- 2022
19. Cefoxitin-based combination for ESBL-producing Enterobacteriaceae endocarditis
- Author
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P, Danneels, C, Rihet, C, Vannier, C, Quinqueneau, R, Courtois, M, Kempf, M, Eveillard, R, Mahieu, and V, Dubée
- Subjects
Endocarditis ,Cilastatin, Imipenem Drug Combination ,Microbial Sensitivity Tests ,beta-Lactamases ,Anti-Bacterial Agents ,Cefoxitin ,Infectious Diseases ,Fosfomycin ,Enterobacteriaceae ,Carbapenems ,Ciprofloxacin ,Urinary Tract Infections ,Escherichia coli ,Humans ,Escherichia coli Infections - Abstract
Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections.We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect.These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.
- Published
- 2022
20. Imipenem cilastatin sodium-associated thrombocytopenia in an older patient: A case report and literature review
- Author
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Weizhen, Qiao, Chunyan, Chang, Qiuhui, Wang, Xiaodong, Cao, and Xiuhong, Zhang
- Subjects
Male ,Pharmacology ,Drug Combinations ,Imipenem ,Cilastatin ,Cilastatin, Imipenem Drug Combination ,Humans ,Thienamycins ,Pharmacology (medical) ,Bacterial Infections ,Thrombocytopenia ,Aged ,Anti-Bacterial Agents - Abstract
Imipenem cilastatin sodium, as a member of a new generation of β-lactam antibiotics, has a broad spectrum of antibacterial activity and a very wide range of application. Thrombocytopenia has been reported as a rare adverse event in several studies of patients treated with imipenem cilastatin sodium. In this study, we present a case of thrombocytopenia associated with imipenem cilastatin sodium in an older patient. The 78-year-old male patient with pulmonary infection was initiated on anti-infection therapy with imipenem cilastatin sodium. On the 9
- Published
- 2022
21. To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia
- Published
- 2012
22. Transcatheter Arterial Embolization Using Imipenem/Cilastatin Sodium for Chronic Low Back Pain Resistant to Conservative Treatment: A Pilot Study with 2-Year Follow-Up
- Author
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Keishi Fujiwara, Yuji Okuno, Koichi Miyazaki, Shohei Inui, Masahiko Shibuya, Eiji Sugihara, and Takayuki Sakugawa
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Cilastatin, Imipenem Drug Combination ,Pilot Projects ,Refractory ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Embolization ,Brief Pain Inventory ,Adverse effect ,Retrospective Studies ,Sacroiliac joint ,business.industry ,Arterial Embolization ,Embolization, Therapeutic ,Low back pain ,Surgery ,Oswestry Disability Index ,Treatment Outcome ,medicine.anatomical_structure ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Low Back Pain ,Follow-Up Studies - Abstract
PURPOSE To evaluate the safety and 2-year follow-up clinical outcomes of transcatheter arterial embolization (TAE) using imipenem/cilastatin sodium for chronic low back pain resistant to conservative treatment. MATERIALS AND METHODS A retrospective review identified 14 patients who underwent TAE for chronic low back pain between October 2017 and August 2018. Patients with low back pain related to the facet or sacroiliac joint, lasting ≥ 6 months, refractory to ≥ 3 months of conservative treatment were eligible for TAE. Each patient received embolization of feeding arteries of painful regions. The changes in brief pain inventory (BPI) scores, adverse events, and the Oswestry Disability Index (ODI) were evaluated at baseline and 1, 3, and 24 months after TAE. Clinical success was defined as BPI maximum pain intensity decrease of ≥ 2 and ODI decrease of ≥ 10 points from baseline. RESULTS Follow-up data were available in 13 and 11 patients, at 3 and 24 months after embolization, respectively. Intention-to-treat clinical success was obtained in 11/14 (79%) of patients at 3 months and 8/14 (57%) of patients at 24 months after TAE. Mean BPI maximum pain intensity and ODI scores decreased significantly from baseline to 1, 3, and 24 months after treatment (7.6 vs.. 4.3, 3.4, and 4.1; 40.8 vs 21.5, 20.0, and 23.8, respectively; all P
- Published
- 2021
23. Intra-Arterial Infusion of Imipenem/Cilastatin Sodium through a Needle Inserted into the Radial Artery as a New Treatment for Refractory Trapeziometacarpal Osteoarthritis
- Author
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Shohei Inui, Shu Yoshizawa, Takao Kaneko, Takanori Shintaku, Hiroyasu Ikegami, and Yuji Okuno
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Radiography ,Cilastatin, Imipenem Drug Combination ,Osteoarthritis ,medicine.disease ,Surgery ,Treatment Outcome ,Refractory ,medicine.artery ,Radial Artery ,Imipenem-Cilastatin Sodium ,medicine ,Humans ,Infusions, Intra-Arterial ,Fluoroscopy ,Radiology, Nuclear Medicine and imaging ,Local anesthesia ,Radial artery ,Cardiology and Cardiovascular Medicine ,business ,Adverse effect - Abstract
PURPOSE To evaluate the efficacy and safety of intra-arterial infusion of temporary embolic material with/without radiographic monitoring via a needle placed into the radial artery to occlude abnormal neovessels for trapeziometacarpal osteoarthritis. MATERIALS AND METHODS Thirty-one patients having Eaton stage II or III osteoarthritis, with a symptom duration longer than 6 months, resistant to conservative therapy for at least 3 months were prospectively enrolled. All procedures were performed by infusing imipenem/cilastatin sodium through a 24-gauge needle that was percutaneously inserted into the radial artery. Seven patients underwent the procedure with fluoroscopy, and 21 patients underwent the procedure without fluoroscopy. The mean Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, numerical rating scale (NRS), and Patient Global Impression of Change (PGIC) scale were evaluated before and at 2, 6, and 24 months after the first procedure. RESULTS Technical success was 100%. The mean procedure time (from the beginning of local anesthesia to the removal of needle) was 2.9 minutes ± 1.6. The QuickDASH score improved from the baseline to 2, 6, and 24 months (49.2 ± 11.2 vs 22.1 ± 11.2, 20.9 ± 16.6, and 19.5 ± 16.1, respectively, all P
- Published
- 2021
24. Aortic endograft infection by Mycobacterium abscessus subsp. massiliense with acquired clarithromycin resistance: a case report.
- Author
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Akiyama Y, Iwamoto N, Kamada K, Yoshida A, Osugi A, Mitarai S, Suzuki T, Yamamoto K, Nagashima M, Horai T, and Ohmagari N
- Subjects
- Male, Humans, Aged, 80 and over, Clarithromycin therapeutic use, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Abscess drug therapy, Macrolides, Drug Resistance, Bacterial, Amikacin therapeutic use, Cilastatin, Imipenem Drug Combination, Stents, Microbial Sensitivity Tests, Mycobacterium abscessus genetics, Mycobacterium Infections, Nontuberculous diagnosis, Mycobacterium Infections, Nontuberculous drug therapy, Mycobacterium Infections, Nontuberculous microbiology
- Abstract
Background: Mycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical site infections, and disseminated diseases, aortic endograft infection has not been reported. Here, we describe the first case of aortic endograft infection caused by MMA., Case Presentation: Two months after stent-graft insertion for an abdominal aortic aneurysm, an 85-year-old man was admitted with fever and abdominal pain and was diagnosed with aortic endograft infection. Despite 14 days of meropenem and vancomycin intravenous administration, periaortic fluid pooling increased as compared to that before antibiotic administration. The abscess was drained, and fluorescent acid-fast staining of the abscess fluid revealed bacilli. We conducted genetic tests on the genes hsp65, rpoB, and sodA, performed Whole Genome Sequencing (WGS), and identified the organism as MMA. Intravenous imipenem-cilastatin (IPM/CS), amikacin (AMK), and oral clarithromycin (CAM) were administered. After 2 months, oral CAM and sitafloxacin were administered because the abscess had decreased in size. However, after 6 weeks, the abscess increased in size again. Antimicrobial susceptibility testing of the drainage fluid from the abscess resulted in the isolation of an MMA strain that had acquired resistance to CAM. Intravenous IPM/CS, AMK, and oral linezolid were added to the treatment regimen along with oral CAM and STFX. However, he was not fully cured and died 6 months later. Neither the full-length erythromycin ribosome methyltransferase (erm)(41) gene nor the rrl or rpIV gene mutations were found by Sanger sequencing in the pre- and post-treatment strains. Whole-genome sequence analysis of the post-treatment strain revealed mutations in genes with no previous reports of association with macrolide resistance., Conclusions: Aortic endograft infection caused by MMA strain is extremely rare; nonetheless, MMA should be suspected as the causative microorganism when broad-spectrum antimicrobials are ineffective., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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25. Increased antibiofilm and growth inhibitory effect of Imipenem/Cilastatin nanoliposomes against clinical Pseudomonas aeruginosa isolates.
- Author
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Milani F, Adibkia K, Hamishehkar H, Gholikhani T, Bani F, and Milani M
- Subjects
- Spectroscopy, Fourier Transform Infrared, Cilastatin, Imipenem Drug Combination, Ethanol, Liposomes, Biofilms, Pseudomonas aeruginosa, Anti-Bacterial Agents pharmacology
- Abstract
Numerous infections are linked to Pseudomonas aeruginosa. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-Pseudomonas aeruginosa effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates' pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm
-1 and 1650 cm-1 , demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics., (© 2023. The Author(s).)- Published
- 2023
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26. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK).
- Author
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Kaye KS, Shorr AF, Wunderink RG, Du B, Poirier GE, Rana K, Miller A, Lewis D, O'Donnell J, Chen L, Reinhart H, Srinivasan S, Isaacs R, and Altarac D
- Subjects
- Adult, Humans, Colistin adverse effects, Cilastatin, Imipenem Drug Combination, Anti-Bacterial Agents adverse effects, beta-Lactamase Inhibitors therapeutic use, Microbial Sensitivity Tests, Acinetobacter baumannii, Pneumonia, Ventilator-Associated drug therapy, Sepsis drug therapy, Pneumonia, Bacterial drug therapy
- Abstract
Background: An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC., Methods: The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046., Findings: Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam-durlobactam group and 20 (32%) of 62 in the colistin group, a difference of -13·2% (95% CI -30·0 to 3·5), which met criteria for non-inferiority. Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam-durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85). Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam-durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam-durlobactam group and 14 (16%) of 86 patients in the colistin group., Interpretation: Our data show that sulbactam-durlobactam was non-inferior to colistin, both agents given in combination with imipenem-cilastatin, for the primary endpoint of 28-day all-cause mortality. Sulbactam-durlobactam was well tolerated and could be an effective intervention to reduce mortality from serious infections caused by carbapenem-resistant ABC, including multidrug-resistant strains., Funding: Entasis Therapeutics and Zai Lab., Competing Interests: Declaration of interests KSK was a member of the data safety monitoring committee for the ATTACK study and has received consulting fees from Entasis Therapeutics, Merck, Shionogi, Qpex Biopharma, GlaxoSmithKline, MicuRx Pharmaceuticals, AbbVie, Johnson & Johnson, Venatorx Pharmaceuticals, and Allecra Therapeutics, and owns stock options in Merck. AFS is a member of the scientific and clinical board for Entasis Therapeutics and has received consulting fees from Entasis Therapeutics. RGW has received consulting fees from Entasis Therapeutics, Venatorx Pharmaceuticals, Merck, and Shionogi, and speaker fees from bioMérieux. The study institutions for BD and RGW received funding from Zai Lab or Entasis Therapeutics, or both, for provision of study materials and drugs. At the time of the study, GEP, KR, AM, DL, JO’D, SS, RI, and DA were employees of Entasis Therapeutics. RI has provided general consulting services to Entasis Therapeutics. At the time of the study, LC and HR were employees of and owned stock in Zai Lab., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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27. Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019
- Author
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Jordan L Kennedy, Jürgen B Bulitta, Kevin Chatham-Stephens, Marissa K Person, Rachel Cook, Thitipong Mongkolrattanothai, Eunjeong Shin, Patricia Yu, Maria E Negron, William A Bower, and Katherine Hendricks
- Subjects
Microbiology (medical) ,Glycopeptides ,Cilastatin, Imipenem Drug Combination ,Levofloxacin ,Amoxicillin-Potassium Clavulanate Combination ,beta-Lactams ,United States ,Anti-Bacterial Agents ,Anthrax ,Lipopeptides ,Infectious Diseases ,Anti-Infective Agents ,Ciprofloxacin ,Tetracyclines ,Bacillus anthracis ,Doxycycline ,Models, Animal ,Animals ,Humans ,Supplement Article - Abstract
Background Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. Methods We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. Results We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. Conclusions These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
- Published
- 2022
28. [Imipenem-cilastatin-relebactam used to treat ventilator-associated pneumonia developing after infection with SARS-CoV-2]
- Author
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Ondřej, Zahornacký, Štefan, Porubčin, Alena, Rovňáková, and Pavol, Jarčuška
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Imipenem ,SARS-CoV-2 ,COVID-19 ,Cilastatin, Imipenem Drug Combination ,Humans ,Pneumonia, Ventilator-Associated ,Microbial Sensitivity Tests ,Azabicyclo Compounds ,Anti-Bacterial Agents - Abstract
The article describes the use of the last-resort carbapenem antibiotic imipenem in combination with relebactam, a novel b-lactamase inhibitor, in the treatment of ventilator-associated pneumonia developing after SARS-CoV-2 infection in a young pregnant patient. The introduction briefly describes the mechanism and spectrum of activity of the antibiotic, including its dosage.
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- 2022
29. Efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations: Results from phase II and III trials
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Wei, Yu, Ping, Shen, Qixia, Luo, Luying, Xiong, and Yonghong, Xiao
- Subjects
Microbiology (medical) ,Drug Combinations ,Clinical Trials, Phase II as Topic ,Infectious Diseases ,Carbapenems ,Clinical Trials, Phase III as Topic ,Immunology ,Cilastatin, Imipenem Drug Combination ,Humans ,Meropenem ,Microbial Sensitivity Tests ,beta-Lactamase Inhibitors ,Microbiology - Abstract
ObjectivesThe addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.MethodsWe conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).ResultsA total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.ConclusionsICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.
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- 2022
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30. Evaluating the usefulness of the estimated glomerular filtration rate for determination of imipenem dosage in critically ill patients
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B Mitton, F Paruk, A Gous, J Chausse, M Milne, P Becker, and M Said
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Adult ,Aged, 80 and over ,Male ,Adolescent ,Critical Illness ,Cilastatin, Imipenem Drug Combination ,General Medicine ,Middle Aged ,Anti-Bacterial Agents ,Imipenem ,South Africa ,Young Adult ,Albumins ,Creatinine ,Sepsis ,Humans ,Female ,Renal Insufficiency, Chronic ,Aged ,Glomerular Filtration Rate - Abstract
Background. Antibiotic dosing in critically ill patients is complicated by variations in the pharmacokinetics of antibiotics in this group. The dosing of imipenem/cilastatin is usually determined by severity of illness and renal function.Objectives. To determine the correlation between estimated glomerular filtration rates (eGFRs) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and imipenem trough levels in critically ill patients.Methods. This prospective observational study was done in the surgical intensive care unit (ICU) at Steve Biko Academic Hospital, Pretoria, South Africa. Imipenem trough levels were measured by high-performance liquid chromatography and compared with eGFRs calculated with the CKD-EPI equation. Correlation was evaluated by the Pearson product-moment correlation coefficient.Results. The study population consisted of 68 critically ill patients aged between 18 and 81 years; 43 (63%) were male, and the mean weight was 78 kg (range 40 - 140). On admission, 30 patients (44%) had sepsis, 16 (24%) were admitted for trauma, and 22 (32%) were admitted for miscellaneous surgical conditions. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ranged from 4 to 39 (mean 18). The 28-day mortality rate was 29%. The mean albumin level was 16 g/L (range 7 - 25), the mean creatinine level 142 μmol/L (range 33 - 840), and the mean eGFR 91 mL/min/1.73 m2 (range 6 - 180). Imipenem trough levels ranged between 3.6 and 92.2 mg/L (mean 11.5). The unadjusted Pearson product-moment correlation coefficient between eGFR and imipenem trough level was –0.04 (p=0.761).Conclusion. Considering the high mortality rate of sepsis in ICUs and the rapid global increase in antimicrobial resistance, it is crucial to dose antibiotics appropriately. Owing to the variability of antibiotic pharmacokinetics in critically ill patients, this task becomes almost impossible when relying on conventional dosing guidelines. This study found that eGFRs do not correlate with imipenem blood levels in critically ill patients and should not be used to determine the dose of imipenem/cilastatin. Instead, the dose should be individualised for patients through routine therapeutic drug monitoring.
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- 2022
31. The safety and efficacy of relebactam/imipenem/cilastatin in Japanese patients with complicated intra-abdominal infection or complicated urinary tract infection: A multicenter, open-label, noncomparative phase 3 study
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Amanda Paschke, Norihiro Aoyama, Fumihiko Yoneyama, Shigeru Kohno, Hiroaki Kikukawa, Hiroyuki Bando, Masayoshi Shirakawa, Kazuya Kawahara, Akiko Takase, and Michelle L Brown
- Subjects
0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Imipenem ,030106 microbiology ,Population ,Cilastatin, Imipenem Drug Combination ,Phases of clinical research ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Adverse effect ,education ,education.field_of_study ,Cilastatin ,business.industry ,Imipenem/cilastatin ,medicine.disease ,Anti-Bacterial Agents ,Systemic inflammatory response syndrome ,Infectious Diseases ,Urinary Tract Infections ,Intraabdominal Infections ,business ,Azabicyclo Compounds ,medicine.drug - Abstract
Introduction Relebactam, a novel class A/C β-lactamase inhibitor developed as a fixed-dose combination with imipenem/cilastatin, restores imipenem activity against imipenem-nonsusceptible gram-negative pathogens. Methods This phase 3, multicenter, open-label, noncomparative study (NCT03293485) evaluated relebactam/imipenem/cilastatin (250 mg/500 mg/500 mg) dosed every 6 h for 5–14 days in Japanese patients with complicated intra-abdominal infections (cIAIs) or complicated urinary tract infections (cUTIs), including those with secondary sepsis. Sepsis was defined as an infection-induced systemic inflammatory response syndrome, with a documented positive blood culture; patients meeting these protocol-defined criteria were evaluated for efficacy against sepsis. Results Of 83 patients enrolled, 81 patients (cIAI, n = 37; cUTI, n = 44) received ≥1 dose of study treatment. Escherichia coli was the most common baseline pathogen isolated in both patients with cIAI and cUTI. Adverse events (AEs) were reported in 74.1% (n = 60/81) of patients, and drug-related AEs occurred in 18.5% (n = 15/81). The most common AEs were diarrhea and nausea (8.6%). Serious AEs occurred in nine patients, including one death, but none were considered treatment related. The primary efficacy endpoint for patients with cIAI was clinical response at end of treatment (EOT) in the microbiologically evaluable (ME) population, and for patients with cUTI was microbiological response at EOT in the ME population. The proportion of cIAI and cUTI patients achieving favorable responses were 85.7% (n = 24/28) and 100.0% (n = 39/39), respectively. All patients with sepsis (cIAI, n = 1; cUTI, n = 5) achieved a favorable composite clinical and microbiological response at EOT. Conclusions A favorable safety and efficacy profile for relebactam/imipenem/cilastatin was observed in Japanese patients with cIAI and cUTI.
- Published
- 2021
32. A Retrospective Comparison of the Efficacy of Embolization with Imipenem/Cilastatin and Microspheres in the Management of Chronic Shoulder Pain.
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Finas M, Frandon J, Gremen E, Horteur C, Benassayag M, Lateur G, Pailhe R, Ferretti G, Bellier A, and Ghelfi J
- Subjects
- Humans, Retrospective Studies, Microspheres, Shoulder Pain therapy, Drug Combinations, Cilastatin, Imipenem Drug Combination, Treatment Outcome, Imipenem therapeutic use, Cilastatin therapeutic use
- Abstract
Purpose: To compare the efficacy of embolization with imipenem/cilastatin and microspheres in chronic shoulder pain., Methods: This retrospective study included 29 patients who underwent embolization for chronic shoulder pain between June 2017 and March 2022 with calibrated MSs from 100 to 250 µm or IMP/CS. The main objective was the clinical success evaluated by the Minimum Clinically Important Difference (MCID) at 3 months after the procedure, validated if the patient responded yes to 2 questions: (1) Is the pain less severe than before the procedure? (2) Are you satisfied with the procedure? The decrease in visual analogue pain scale scores and the safety of the procedure were evaluated., Results: Embolization was achieved in all patients. In the MS group, 4/15 patients (26.7%) experienced clinical success at 3 months according to MCID versus 10/14 patients (71.4%) in the IMP/CS group (p = 0.02). The mean VAS decreases were respectively - 28.6% ± 34.6 in the MS group and - 36.8% ± 27.8 in the IMP/CS group at 1 month (p = 0.50), - 29.9% ± 29.0 and - 39.6% ± 23.0 at 3 months (p = 0.33) and - 30.6% ± 32.8 and - 46.6% ± 28.4 at 6 months after the procedure (p = 0.26). Eleven patients (73.3%) in the MS group and 3 patients (21.4%) in the IMP/CS group had complications (p = 0.01). Among them, 2/15 patients (13.3%) had transient skin ischaemia in the MS group., Conclusion: Embolization with IMP/CS may be more effective and safer than MSs in the management of chronic shoulder pain., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)
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- 2023
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33. Pustulosis exantematosa generalizada aguda
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Saavedra, Susan, Briceño, Mónica, Pajuelo, Gabriela, and Sandoval, Betty
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Pustulosis Exantematosa Generalizada Aguda ,Ceftriaxona ,Acute Generalized Exanthematous Pustulosis ,Ceftriaxone ,Combinación Cilastatina e Imipenem ,Cilastatin, Imipenem Drug Combination - Abstract
Acute generalized exanthematic pustulosis (PEGA) is a rare dermatological pathology characterized by the sudden and generalized appearance of multiple, sterile, non-follicular, punctate pustules on an erythematous and edematous base. It is frequently triggered by drugs, among which antibiotics stand out. We present the case of a 40-year-old male patient who was admitted to the emergency room due to abdominal pain síndrome, to rule out intra-abdominal tumor pathology, initially indicating ceftriaxone and metronidazole. The next day, he was re-admitted to the emergency room, finding, after emergency surgery, acute appendicitis complicated with intestinal perforation, for which they rotated the antibiotic therapy to imipenem-cilastatin + metronidazole. At the next 48 hours, he presents generalized erythema and some small pustules and microvesicles in the thoracic region, upper extremities and neck. Likewise, it is shown in laboratory tests, neutrophilic leukocytosis and hypoalbuminemia. In the biopsy, subcorneal and intraepidermal neutrophilic pustules are found, with edematous papillary dermis and perivascular inflammatory infiltrate with the presence of neutrophils and few eosinophils. With everything described above, we reached the conclusion of a PEGA, triggered by received antibiotics, ceftriaxone or imipenemcilastatin. After 6 days of the suspension of imipenem-cilastatin, the patient shows improvement of dermal lesions, with mild erythema and scant fine scaling., La pustulosis exantematosa generalizada aguda (PEGA) es una patología dermatológica poco frecuente, caracterizada por la aparición brusca y generalizada de múltiples pústulas puntiformes, estériles, no foliculares, sobre una base eritematosa y edematosa. Es desencadenada frecuentemente por fármacos, entre los cuales resaltan los antibióticos. Presentamos el caso de un paciente varón de 40 años, que ingresó a emergencia por síndrome doloroso abdominal a descartar patología tumoral intraabdominal, indicándole inicialmente ceftriaxona y metronidazol. Al día siguiente, reingresó a emergencia encontrando, tras la cirugía de emergencia, una apendicitis aguda complicada con perforación intestinal, por lo cual rotan la antibioticoterapia a imipenem-cilastatina + metronidazol. A las siguientes 48 horas, presentó eritema generalizado y algunas pústulas pequeñas y microvesículas en región torácica, extremidades superiores y cuello. Asimismo, se observó en los exámenes de laboratorio, leucocitosis neutrofílica e hipoalbuminemia. En la biopsia, se encontró pústulas neutrofílicas subcorneales e intraepidérmicas, con dermis papilar edematosa e infiltrado inflamatorio perivascular con presencia de neutrófilos y escasos eosinófilos. Con todo lo descrito anteriormente, llegamos a la conclusión de una PEGA, desencadenado por los antibióticos recibidos, ceftriaxona o imipenem-cilastatina. Tras 6 días de la suspensión de imipenem-cilastatina, paciente mostró mejoría de lesiones dérmicas, con leve eritema y escasa descamación fina.
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- 2022
34. In vitrointeractions of ambroxol hydrochloride or amlodipine in combination with antibacterial agents against carbapenem‐resistantAcinetobacter baumannii
- Author
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Decai Wang, Yuehua Wang, Xiuyun Li, Shujuan Sun, and Chunyan Lu
- Subjects
Acinetobacter baumannii ,0106 biological sciences ,Drug ,media_common.quotation_subject ,Cefoperazone ,Cilastatin, Imipenem Drug Combination ,Microbial Sensitivity Tests ,Tigecycline ,Drug resistance ,Pharmacology ,01 natural sciences ,Applied Microbiology and Biotechnology ,Meropenem ,03 medical and health sciences ,010608 biotechnology ,Drug Resistance, Bacterial ,polycyclic compounds ,medicine ,Humans ,Biapenem ,media_common ,0303 health sciences ,biology ,030306 microbiology ,Chemistry ,Drug Synergism ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,In vitro ,Anti-Bacterial Agents ,Ambroxol ,Drug Combinations ,Carbapenems ,Sulbactam ,Thienamycins ,Amlodipine ,Polymyxin B ,Acinetobacter Infections ,medicine.drug - Abstract
The aim of this study was to investigate the in vitro interactions of ambroxol hydrochloride (ABH) or amlodipine (AML) with commonly used antibacterial agents, including meropenem, imipenem-cilastatin sodium, biapenem, cefoperazone-sulbactam, polymyxin B, and tigecycline, against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. Drug interactions were interpreted using two models, that is, the fractional inhibitory concentration index (FICI) model and the percentage of growth difference (ΔE) model. The results show that a majority of the combination groups exhibited partial synergy and additive interactions, such as the combinations of carbapenems and cefoperazone-sulbactam (SCF) with ABH or AML. While the combination of PB/AML exhibited synergistic interactions against all tested isolates, and PB/ABH exhibited synergistic interactions against two isolates. The FICI and ΔE model correlated very well for the combinations of PBABH and PB/AML against AB2. The combinations of TGC with ABH or AML mainly exhibited additive and indifferent interactions. There were no antagonistic interactions observed in any of the combinations. In conclusion, this study revealed that the non-antibacterial agents ABH or AML can work synergistically or partial synergistically with antibacterial agents against CRAB. This finding is crucial for overcoming the carbapenem resistance of A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: Drug combination is an effective approach for the treatment of resistant bacterial infection. The significance of using drug combination is that it can reduce drug dosage requirements, reduce the toxic effects of agents and prevent or delay the emergence of drug resistance. This study measured the in vitro interactions between non-antimicrobial agents and antibacterial agents against carbapenem-resistant Acinetobacter baumannii and the results of this study provide new insight to find strategies to overcome the carbapenem resistance in A. baumannii.
- Published
- 2019
35. Investigating the need for therapeutic drug monitoring of imipenem in critically ill patients: Are we getting it right?
- Author
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B, Mitton, F, Paruk, A, Gous, J, Chausse, M, Milne, P, Becker, and M, Said
- Subjects
Adult ,Aged, 80 and over ,Male ,Intensive Care Units ,Adolescent ,Critical Illness ,Cilastatin, Imipenem Drug Combination ,Humans ,Female ,Prospective Studies ,Middle Aged ,Aged ,Anti-Bacterial Agents - Abstract
The drug levels and clearances of imipenem in critically ill patients are not comprehensively described in current literature, yet it is vital that adequate levels be achieved for therapeutic success.To determine the proportion of critically ill patients treated with imipenem/cilastatin with sub-therapeutic imipenem plasma levels, and to compare the clinical outcomes of those patients with therapeutic levels with those who had sub-therapeutic levels.Trough imipenem plasma levels of 68 critically ill patients from a surgical intensive care unit were measured using a validated high-performance liquid chromatography method. Imipenem trough levels were compared with the minimum inhibitory concentration (MIC) of the causative bacterial agents, based on a target value of 100% time above MIC (¦Tgt;MIC).The proportion of participants with sub-therapeutic imipenem levels was 22% (95% confidence interval (CI) 13% - 34%). The 14- and 28-day mortality rates in the sub-therapeutic group were 33% and 40%, respectively, compared with 19% (p=0.293) and 26% (p=0.346), respectively, in the therapeutic group. Sub-therapeutic imipenem plasma levels are associated with adjusted hazard ratio of 1.47 (95% CI 0.55 - 3.91).The lower proportion of critically ill patients with sub-therapeutic imipenem plasma levels in this study compared with previous studies may be attributed to the practice of higher dosages and the administration method of extended infusions of imipenem/cilastatin in our setting. The results demonstrate a trend of higher mortality in patients with sub-therapeutic imipenem levels, although the results were not statistically significant at this sample size.
- Published
- 2021
36. Who gets treated for influenza: A surveillance study from the US Food and Drug Administration's Sentinel System
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Robert Orr, Catherine A. Panozzo, Greg Measer, Nicole Haug, Henry Francis, Sarah K. Dutcher, Alfred Sorbello, Noelle M. Cocoros, Austin Cosgrove, Sengwee Toh, and Crystal Garcia
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Epidemiology ,medicine.medical_treatment ,Cilastatin, Imipenem Drug Combination ,Medicare ,Antiviral Agents ,Diabetes mellitus ,Influenza, Human ,medicine ,Humans ,Asthma ,Aged ,Retrospective Studies ,Mechanical ventilation ,business.industry ,United States Food and Drug Administration ,Retrospective cohort study ,medicine.disease ,Obesity ,United States ,Vaccination ,Hospitalization ,Oxygen ,Infectious Diseases ,Emergency medicine ,Complication ,business ,Medicaid - Abstract
Objective:We describe the baseline characteristics and complications of individuals with influenza in the US FDA’s Sentinel System by antiviral treatment timing.Design:Retrospective cohort design.Patients:Individuals aged ≥6 months with outpatient diagnoses of influenza in June 2014–July 2017, 3 influenza seasons.Methods:We identified the comorbidities, vaccination history, influenza testing, and outpatient antiviral dispensings of individuals with influenza using administrative claims data from 13 data partners including the Centers for Medicare and Medicaid Services, integrated delivery systems, and commercial health plans. We assessed complications within 30 days: hospitalization, oxygen use, mechanical ventilation, critical care, ECMO, and death.Results:There were 1,090,333 influenza diagnoses in 2014–2015; 1,005,240 in 2016–2017; and 578,548 in 2017–2018. Between 49% and 55% of patients were dispensed outpatient treatment within 5 days. In all periods >80% of treated individuals received treatment on the day of diagnosis. Those treated on days 1–5 after diagnosis had higher prevalences of diabetes, chronic obstructive pulmonary disease, asthma, and obesity compared to those treated on the day of diagnosis or not treated at all. They also had higher rates of hospitalization, oxygen use, and critical care. In 2014–2015, among those aged ≥65 years, the rates of hospitalization were 45 per 1,000 diagnoses among those treated on day 0; 74 per 1,000 among those treated on days 1–5; and 50 per 1,000 among those who were untreated.Conclusions:In a large, national analysis, approximately half of people diagnosed with influenza in the outpatient setting were treated with antiviral medications. Delays in outpatient dispensed treatment were associated with higher prevalence of comorbidities and higher rates of complication.
- Published
- 2021
37. Two-year outcomes comparing Embosphere® microspheres versus Imipenem Cilastatin for genicular artery embolization in patients with moderate to severe knee osteoarthritis.
- Author
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Bhatia S, Jalaeian H, Kumar J, Acharya V, Shibuya M, Bhatia A, and Okuno Y
- Subjects
- Humans, Cilastatin, Imipenem Drug Combination, Microspheres, Retrospective Studies, Treatment Outcome, Pain drug therapy, Pain etiology, Arteries, Osteoarthritis, Knee drug therapy
- Abstract
Background: Genicular artery embolization (GAE) is a novel technique and has the potential to provide midterm relief of pain for patients with mild-to-moderate knee osteoarthritis resistant to conservative management. This study compares the efficacy and safety of trisacryl gelatin microspheres to Imipenem/Cilastatin particles for GAE with 2 years of clinical follow-up., Methods: In this retrospective study, eight patients with knee osteoarthritis (11 knees) who underwent GAE with 100-300 μm trisacryl gelatin microspheres particles were compared with six patients (nine knees) who underwent GAE with Imipenem/Cilastatin particles. Clinical outcomes were evaluated at 3-month and 24-month follow-ups and compared to baseline using the WOMAC questionnaire., Results: The median follow-up was 796 days (range: 736-808). There were no significant differences in clinical outcome measures at the 3-month or 24-month follow-up. Both embolic materials resulted in a decrease in Pain WOMAC and Total WOMAC scores at 3 months (p < 0.05), and the effect of treatment on Pain WOMAC and Total WOMAC score reduction was sustained until the 24-month follow-up (p < 0.05). Minor events (Clavien-Dindo classification grade I) included transient cutaneous color change (n = 3) and transient leg numbness (n = 1) after embolization with trisacryl gelatin microspheres particles (p = 0.08). All minor adverse events resolved spontaneously. There were no major adverse events., Conclusion: One hundred to three hundred μm trisacryl gelatin microspheres particles can be considered for genicular artery embolization and is comparable to Imipenem/Cilastatin particles in pain reduction of moderate to severe knee osteoarthritis. A sustained effect is observed for up to 2 years of follow-up., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shivank Bhatia reports a relationship with Embolx that includes: consulting or advisory. Shivank Bhatia reports a relationship with Merit Medical Systems Inc that includes: consulting or advisory, funding grants, and travel reimbursement. Yuji Okuno reports a relationship with Asahi Intecc Co Ltd that includes: consulting or advisory, funding grants, and speaking and lecture fees., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2023
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38. Embolization for Osteoarthritic Pain: Ready to Cross the Chasm?
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Neeral R Patel, Sebastian Mafeld, and Michael N. Patlas
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medicine.medical_specialty ,Neovascularization, Pathologic ,business.industry ,medicine.medical_treatment ,Synovial Membrane ,Cilastatin, Imipenem Drug Combination ,Pain ,General Medicine ,Osteoarthritis, Knee ,Embolization, Therapeutic ,Surgery ,medicine ,Humans ,Pain Management ,Protease Inhibitors ,Radiology, Nuclear Medicine and imaging ,Embolization ,business - Published
- 2020
39. Defining the Role of Novel β-Lactam Agents That Target Carbapenem-Resistant Gram-Negative Organisms
- Author
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Alice J. Hsu and Pranita D. Tamma
- Subjects
0301 basic medicine ,Tazobactam ,medicine.medical_specialty ,medicine.drug_class ,Avibactam ,030106 microbiology ,Antibiotics ,Cilastatin, Imipenem Drug Combination ,Tigecycline ,Aztreonam ,Ceftazidime ,Heterocyclic Compounds, 1-Ring ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Resistance, Multiple, Bacterial ,Gram-Negative Bacteria ,polycyclic compounds ,medicine ,030212 general & internal medicine ,Intensive care medicine ,Organism ,Invited Review ,business.industry ,Meropenem ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,Ceftazidime/avibactam ,Boronic Acids ,Anti-Bacterial Agents ,Cephalosporins ,Drug Combinations ,Infectious Diseases ,Carbapenems ,chemistry ,Infectious disease (medical specialty) ,Pediatrics, Perinatology and Child Health ,Colistin ,Gram-Negative Bacterial Infections ,business ,Azabicyclo Compounds ,medicine.drug - Abstract
With the current carbapenem-resistant organism crisis, conventional approaches to optimizing pharmacokinetic-pharmacodynamic parameters are frequently inadequate, and traditional salvage agents (eg, colistin, tigecycline, etc) confer high toxicity and/or have low efficacy. However, several β-lactam agents with activity against carbapenem-resistant organisms were approved recently by the US Food and Drug Administration, and more are anticipated to be approved in the near future. The primary goal of this review is to assist infectious disease practitioners with preferentially selecting 1 agent over another when treating patients infected with a carbapenem-resistant organism. However, resistance to some of these antibiotics has already developed. Antibiotic stewardship programs can ensure that they are reserved for situations in which other options are lacking and are paramount for the survival of these agents.
- Published
- 2019
40. Alteration in Acute Kidney Injury Potential with the Combination of Vancomycin and Imipenem-Cilastatin/Relebactam or Piperacillin/Tazobactam in a Preclinical Model
- Author
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Manjunath P. Pai, Aleksas Matvekas, Ernane Souza, Ryan L. Crass, and Miao He
- Subjects
Male ,medicine.medical_specialty ,Urology ,Cilastatin, Imipenem Drug Combination ,Tazobactam ,Nephrotoxicity ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Vancomycin ,polycyclic compounds ,medicine ,Animals ,Pharmacology (medical) ,030212 general & internal medicine ,Blood urea nitrogen ,Retrospective Studies ,Pharmacology ,0303 health sciences ,Creatinine ,030306 microbiology ,business.industry ,Imipenem/cilastatin ,Acute kidney injury ,Acute Kidney Injury ,medicine.disease ,Anti-Bacterial Agents ,Mice, Inbred C57BL ,Piperacillin, Tazobactam Drug Combination ,Infectious Diseases ,chemistry ,Piperacillin/tazobactam ,Drug Therapy, Combination ,business ,Azabicyclo Compounds ,Piperacillin ,medicine.drug - Abstract
Background: This risk of vancomycin (VAN)-associated acute kidney injury (AKI) may be altered with combination regimens. The specific AKI risk when VAN is combined with imipenem-cilastatin/relebactam (IMP-C/REL) or piperacillin/tazobactam (TZP) has not been clearly defined.Objectives: To quantify the dose-AKI relationships of VAN alone and in combination with TZP or imipenem-cilastatin/relebactam (IMP-C/REL).Methods: Ten to twelve week old male C57BL/6J mice (Charles River Laboratory) were dosed with study drug regimens in three stages. Stage 1 consisted of a VAN dose-ranging design (0-600 mg/kg/day) over a 7-day period to identify the VAN monotherapy dose-AKI relationship in the murine model. Stage 2 evaluated the approximate VAN dose eliciting 50% AKI response in Stage 1 in combination with the highest human equivalent doses (HED) used in pre-clinical murine models (2.5 g/kg/day of TZP, 320 mg/kg/day of IMP-C/REL). Stage 3 tested these combinations with fractionated doses of TZP or IMP-C/REL administered at 6- and 12-hour intervals. In these studies, AKI was defined both by biomarkers (serum creatinine [SCr], blood urea nitrogen [BUN]) and histopathological assessment by a treatment-blinded pathologist.Results: VAN doses of 300 to 500 mg/kg/day reproducibly led to development of AKI within 4 days of dosing. Mice treated with VAN alone had a near doubling of their baseline SCr and BUN compared to control, IMP-C/REL alone, or TZP alone. Both VAN+IMP-C/REL and VAN+TZP had significantly (p
- Published
- 2021
41. Imipenem/cilastatin/relebactam: A new carbapenem β-lactamase inhibitor combination
- Author
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Ahmad El Ouweini, Lamis R. Karaoui, Hanine Mansour, and Elias B. Chahine
- Subjects
Adult ,Imipenem ,medicine.medical_specialty ,Carbapenem ,Adolescent ,Cilastatin, Imipenem Drug Combination ,Microbial Sensitivity Tests ,Tazobactam ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,polycyclic compounds ,Medicine ,Humans ,030212 general & internal medicine ,Pharmacology ,0303 health sciences ,Cilastatin ,biology ,030306 microbiology ,business.industry ,Health Policy ,Imipenem/cilastatin ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,Acinetobacter baumannii ,Anti-Bacterial Agents ,Carbapenems ,Colistin ,business ,Azabicyclo Compounds ,medicine.drug ,Piperacillin - Abstract
Purpose The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of imipenem/cilastatin/relebactam are reviewed. Summary Imipenem/cilastatin/relebactam is a newly approved anti-infective combination of a well-established β-lactam and a new β-lactamase inhibitor for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by susceptible gram-negative bacteria in patients 18 years of age or older with limited or no alternative treatment options. The antibiotic is also indicated for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The antibiotic is active in vitro against a wide range of pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales (CRE) such as Klebsiella pneumoniae carbapenemase. The addition of relebactam does not restore the activity of imipenem against metallo-β-lactamase (MBL)–producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. Two phase 3 clinical trials of imipenem/cilastatin/relebactam were conducted. In the RESTORE-IMI 1 trial, the efficacy and safety of imipenem/cilastatin/relebactam was found to be comparable to that of imipenem/cilastatin plus colistin for the treatment of infections caused by imipenem-nonsusceptible gram-negative bacteria in patients with HABP/VABP, cUTIs, and cIAIs, with a significantly lower incidence of nephrotoxicity reported with the new antibiotic. The RESTORE-IMI 2 trial demonstrated the noninferiority of imipenem/cilastatin/relebactam to piperacillin/tazobactam for the treatment of HABP/VABP. Commonly reported adverse events in clinical trials included anemia, elevated liver enzymes, electrolyte imbalances, nausea, vomiting, diarrhea, headache, fever, phlebitis and/or infusion-site reactions, and hypertension. Conclusion Imipenem/cilastatin/relebactam is a new β-lactam/β-lactamase inhibitor combination with activity against MDR gram-negative bacteria, including many CRE but excluding MBL-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. It is approved for the treatment of cUTIs, cIAIs, and HABP/VABP.
- Published
- 2021
42. Characteristics of Imipenem/Cilastatin: Considerations for Musculoskeletal Embolotherapy
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Kierdra I. Dowling, Naomi Matsuura, Robert Koucheki, Neeral R Patel, and Sebastian Mafeld
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Drug Combinations ,Cilastatin ,business.industry ,Anesthesia ,Imipenem/cilastatin ,Medicine ,Cilastatin, Imipenem Drug Combination ,Humans ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,business ,Embolization, Therapeutic ,medicine.drug - Published
- 2021
43. Challenges in Treating
- Author
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Divita, Singh, Mikayla, Johnson, Caleah S, Kitchens, and Andrew, Boone
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Mycobacterium abscessus ,Clarithromycin ,Cilastatin, Imipenem Drug Combination ,Humans ,Microbial Sensitivity Tests ,Mycobacterium chelonae ,Anti-Bacterial Agents ,Mycobacterium - Abstract
Prosthetic joint infections (PJIs) remain a major complication of arthroplasty, most of which are caused by
- Published
- 2020
44. Advances in novel antibiotics to treat multidrug-resistant gram-negative bacterial infections
- Author
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Brit Long, Aaron Matlock, Kayvan Moussavi, Joshua Garcia, and Stephen Y. Liang
- Subjects
medicine.medical_specialty ,Tazobactam ,medicine.drug_class ,Avibactam ,Antibiotics ,Resistance ,Cilastatin, Imipenem Drug Combination ,030204 cardiovascular system & hematology ,Plazomicin ,Ceftazidime ,03 medical and health sciences ,chemistry.chemical_compound ,Heterocyclic Compounds, 1-Ring ,0302 clinical medicine ,Antibiotic resistance ,Acute care ,EM - Review ,Omadacycline ,Gram-Negative Bacteria ,Internal Medicine ,Medicine ,Humans ,Multidrug-resistant ,030212 general & internal medicine ,Intensive care medicine ,Novel ,business.industry ,Meropenem ,Eravacycline ,Boronic Acids ,Drug Resistance, Multiple ,Anti-Bacterial Agents ,Cephalosporins ,Drug Combinations ,chemistry ,Tetracyclines ,Drug Design ,Emergency Medicine ,Sisomicin ,Ceftolozane ,business ,Gram-Negative Bacterial Infections ,Azabicyclo Compounds - Abstract
Antimicrobial resistance is a growing threat to public health and an increasingly common problem for acute care physicians to confront. Several novel antibiotics have been approved in the past decade to combat these infections; however, physicians may be unfamiliar with how to appropriately utilize them. The purpose of this review is to evaluate novel antibiotics active against resistant gram-negative bacteria and highlight clinical information regarding their use in the acute care setting. This review focuses on novel antibiotics useful in the treatment of infections caused by resistant gram-negative organisms that may be seen in the acute care setting. These novel antibiotics include ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilistatin/relebactam, cefiderocol, plazomicin, eravacycline, and omadacycline. Acute care physicians should be familiar with these novel antibiotics so they can utilize them appropriately.
- Published
- 2020
45. Elevated serum β-d-glucan levels in cavitary pulmonary nocardiosis
- Author
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Kyoko Yagyu, Yuko Nakatsuji, and Haruhiko Matsushita
- Subjects
0301 basic medicine ,Palliative care ,beta-Glucans ,Colorectal cancer ,Cilastatin, Imipenem Drug Combination ,Chest pain ,Gastroenterology ,Dexamethasone ,0302 clinical medicine ,030212 general & internal medicine ,infections ,Aged, 80 and over ,biology ,Sulfamethoxazole ,Nocardia ,General Medicine ,Reminder of Important Clinical Lesson ,pneumonia (infectious disease) ,Anti-Bacterial Agents ,Treatment Outcome ,Female ,Proteoglycans ,medicine.symptom ,Colorectal Neoplasms ,medicine.drug ,medicine.medical_specialty ,030106 microbiology ,Nocardia Infections ,Antineoplastic Agents ,03 medical and health sciences ,Internal medicine ,Trimethoprim, Sulfamethoxazole Drug Combination ,medicine ,Humans ,Cilastatin ,business.industry ,medicine.disease ,biology.organism_classification ,Trimethoprim ,pneumonia (respiratory medicine) ,business - Abstract
An 86-year-old woman with Borrmann type III colorectal cancer (Union for International Cancer Control pT4aN2bM1c, pStage IVc) had received dexamethasone for the last 6 months as palliative care. She presented with a low-grade fever, chest pain and cough. Chest radiography on admission showed cavities and consolidations bilaterally in the upper lobes. A blood examination on admission revealed highly elevated serum β-d-glucan levels. The diagnosis by bronchoscopy was pulmonary nocardiosis. With trimethoprim/sulfamethoxazole and imipenem/cilastatin, the β-d-glucan levels were decreased, and chest X-ray showed improvement after 1 month. β-d-glucan is known to be a biomarker of fungal infection. It is possible that β-d-glucan levels also indicate a pulmonary infection by Nocardia.
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- 2020
46. [One case of severely scalded patient with pneumonia and sepsis]
- Author
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W Z, Zhang, Y, Miao, and X L, Zou
- Subjects
Male ,Sepsis ,Pseudomonas aeruginosa ,Cilastatin, Imipenem Drug Combination ,Humans ,Pneumonia ,Middle Aged ,Burns ,Anti-Bacterial Agents - Abstract
In February 2018, one 54-year-old male patient with severe scald complicated with pneumonia and sepsis was transferred to Qingdao Municipal Hospital from other hospital. Drugs including cephalosporin, vancomycin, and imipenem/cilastatin combined with ciprofloxacin were used successively for anti-infective treatment, with no obvious effect. Multiple bacterial culture results of sputum, blood, and wound exudate showed infection of extensively drug resistant2018年2月,青岛市市立医院收治1例经外院转入的严重烫伤合并肺炎和脓毒症的54岁男性患者。先后使用头孢菌素、万古霉素、亚胺培南/西司他丁+环丙沙星等抗感染治疗,但无明显效果。痰液、血液及创面分泌物多次细菌培养结果提示泛耐药铜绿假单胞菌感染。入院第4天调整抗感染治疗方案,补充血浆、红细胞及白蛋白,行营养支持及对症处理,同时进行用药监护,关注药物相关不良反应。经过10余天的治疗,患者感染得到有效控制,病情逐渐好转。本病例提示,严重烧伤患者易发生严重且致命的全身性感染,抗菌药物的不规范使用增加了泛耐药菌的感染风险,清晰的抗感染思路和抗菌药物的有效应用有助于提高感染治疗的成功率,对改善严重烧伤患者的预后具有重要价值。.
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- 2020
47. Comparative review of imipenem/cilastatin versus meropenem
- Author
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P. Chavanet, A. Salmon-Rousseau, Marielle Buisson, C. Martins, Lionel Piroth, M. Blot, S. Mahy, Département d'infectiologie (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
- Subjects
Carbapenem ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Cilastatin, Imipenem Drug Combination ,Gram-Positive Bacteria ,Meropenem ,03 medical and health sciences ,Drug Stability ,Pregnancy ,Drug Resistance, Multiple, Bacterial ,Gram-Negative Bacteria ,polycyclic compounds ,medicine ,Humans ,Pregnancy Complications, Infectious ,Intensive care medicine ,Adverse effect ,Child ,Biotransformation ,0303 health sciences ,Molecular Structure ,030306 microbiology ,business.industry ,Imipenem/cilastatin ,Contraindications, Drug ,Infant ,Drug Resistance, Microbial ,Bacterial Infections ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,3. Good health ,Anti-Bacterial Agents ,Infectious Diseases ,Organ Specificity ,Pharmacodynamics ,Child, Preschool ,bacteria ,Antibiotic Stewardship ,Female ,business ,Liver Failure ,medicine.drug ,Protein Binding - Abstract
Introduction Carbapenems are broad-spectrum antibacterial molecules. Imipenem-cilastatin and meropenem are the two main molecules used in French healthcare services. Objective We aimed to evaluate the relative strengths and weaknesses of these two molecules by considering their pharmacokinetic, pharmacodynamic, microbiological, and clinical properties. We demonstrated that imipenem-cilastatin and meropenem are not alike. Method Review of the literature by querying the MEDLINE network. Results Imipenem-cilastatin is the first marketed molecule of the carbapenem class. It is more effective against Gram-positive cocci. Its stability does not allow for long infusions and its main adverse effect on the central nervous system limits its use. Meropenem is more effective against Gram-negative bacilli. Its stability and its milder adverse effects distinguish it from imipenem-cilastatin. Conclusion Meropenem is preferred for daily use in healthcare services when carbapenems are to be used.
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- 2020
48. Safety, Pharmacokinetics, and Drug-Drug Interaction Potential of Intravenous Durlobactam, a β-Lactamase Inhibitor, in Healthy Subjects
- Author
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John O'Donnell, Jason D. Lickliter, Robin Isaacs, and Kenneth Lawrence
- Subjects
0301 basic medicine ,030106 microbiology ,Drug-drug interaction ,Cilastatin, Imipenem Drug Combination ,β-lactamases ,Urine ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,β lactamase inhibitor ,Pharmacokinetics ,polycyclic compounds ,Humans ,Medicine ,Drug Interactions ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,biology ,business.industry ,Healthy subjects ,Sulbactam ,biology.organism_classification ,Healthy Volunteers ,Anti-Bacterial Agents ,Acinetobacter baumannii ,Infectious Diseases ,Renal physiology ,beta-Lactamase Inhibitors ,business ,pharmacokinetics ,medicine.drug - Abstract
Durlobactam (DUR; also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem-cilastatin (IMI-CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In part A, subjects, including a cohort of elderly subjects (which received DUR at 1 g), received single ascending doses of DUR ranging from 0., Durlobactam (DUR; also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem-cilastatin (IMI-CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In part A, subjects, including a cohort of elderly subjects (which received DUR at 1 g), received single ascending doses of DUR ranging from 0.25 to 8 g. In part B, multiple ascending doses of DUR ranging from 0.25 to 2 g were administered every 6 h (q6h) for 29 doses. In parts C and D, the drug-drug interaction (DDI) potential, including the safety, of DUR (1 g) with SUL (1 g) and/or IMI-CIL (0.5/0.5 g) was investigated after single and multiple doses. Plasma and urine concentrations of DUR, SUL, and IMI-CIL were determined. Among 124 subjects, DUR was generally safe and well tolerated when it was administered either alone or in combination with SUL and/or IMI-CIL. After single and multiple doses, DUR demonstrated linear dose-proportional exposure across the studied dose ranges. Renal excretion was a predominant clearance mechanism. No drug-drug interaction potential between DUR and SUL and/or IMI-CIL was identified. SUL-DUR at 1 g (of each component) administered q6h with a 3-h intravenous (i.v.) infusion is under development for the treatment of serious infections due to A. baumannii. (This study has been registered at ClinicalTrials.gov under identifier NCT02971423.)
- Published
- 2020
49. The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients
- Author
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Tori, Katerina, Tansarli, Giannoula S., Parente, Diane M., Kalligeros, Markos, Ziakas, Panayiotis D., and Mylonakis, Eleftherios
- Subjects
antipseudomonal beta-lactams ,Neutropenia ,empirical treatment ,Fever ,Economic Evaluation Study ,Cost-Benefit Analysis ,Cilastatin, Imipenem Drug Combination ,Health Care Costs ,Meropenem ,solid tumors ,Anti-Bacterial Agents ,Decision Support Techniques ,febrile neutropenia ,Piperacillin, Tazobactam Drug Combination ,Treatment Outcome ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Humans ,Computer Simulation ,hematological malignancies ,Cefepime ,cost-effectiveness ,Research Article - Abstract
Supplemental Digital Content is available in the text, Purpose: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. Methods: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. Results: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. Discussion: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.
- Published
- 2020
50. Imipenem/cilastatin sodium/relebactam fixed combination to treat urinary infections and complicated intra-abdominal bacterial infections
- Author
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Arunava Dasgupta, Ritesh P. Thakare, and Sidharth Chopra
- Subjects
Adult ,medicine.medical_specialty ,Imipenem ,medicine.drug_class ,Urinary system ,Antibiotics ,Cilastatin, Imipenem Drug Combination ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Imipenem-Cilastatin Sodium ,medicine ,Relebactam ,Humans ,Cilastatin ,business.industry ,Cilastatin sodium ,Bacterial Infections ,Anti-Bacterial Agents ,Infectious disease (medical specialty) ,Urinary Tract Infections ,Intraabdominal Infections ,business ,Azabicyclo Compounds ,medicine.drug - Abstract
Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and β-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative microorganisms in adult patients with limited or no alternative treatment options. The product was also approved by the European Medicines Agency (EMA) in 2020 for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.
- Published
- 2020
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