Critical Review of Double-Carbapenem Therapy for the Treatment of Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 53 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Ola Mashni ◽  
Lama Nazer ◽  
Jennifer Le
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Studies ◽  
Case Reports ◽  
Therapeutic Option ◽  
Data Extraction ◽  
Gastrointestinal Symptoms ◽  
Current Data ◽  
Study Selection

Objective: To review the clinical data on the effectiveness and safety of double carbapenem therapy (DCT) in patients infected with carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Data Sources: A literature search was performed utilizing PubMed and EMBASE (from 1966 to May 2018); bibliographies of the retrieved articles were also searched. Study Selection and Data Extraction: Articles were included if they evaluated patients with infections caused by CP-Kp and were treated with DCT. Meeting abstracts, editorials, and animal and in vitro studies were excluded. Data Synthesis: The search strategy revealed 8 case reports and 6 clinical studies (total of 171 patients) that evaluated the administration of ertapenem followed by prolonged infusions of meropenem or doripenem. Most patients were critically ill and commonly had infections in the blood, lungs, and urine. Clinical and microbiological success were reported in 70% of the patients and mortality in 24%. Adverse events, which included mostly seizures, sodium disorders, and gastrointestinal symptoms, were reported in 16 patients; none required interruption of treatment. Relevance to Patient Care and Clinical Practice: This review evaluated the clinical experience of DCT in the treatment of CP-Kp infections, based on case reports and clinical studies, for the potential role of DCT as a therapeutic option. Conclusion: Despite the limited studies, current data suggest that DCT may be an effective and safe strategy to treat CP-Kp. However, large randomized controlled trials are necessary to clearly define the role of DCT.

Predicting Inhibitory Drug—Drug Interactions and Evaluating Drug Interaction Reports Using Inhibition Constants

2005 ◽  
Vol 39 (6) ◽  
pp. 1064-1072 ◽  
Author(s):  
Kenneth A Bachmann ◽  
Jeffrey D Lewis
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Web Sites ◽  
Case Reports ◽  
Data Extraction ◽  
Data Sources ◽  
Study Selection ◽  
Inhibitory Drug

OBJECTIVE: To review the use of inhibitory constants (Ki) determined from in vitro experiments in the prediction of the significance of inhibitory drug—drug interactions (DDIs). DATA SOURCES: Searches of MEDLINE (1966—August 2004) and manual review of journals, conference proceedings, reference textbooks, and Web sites were performed using the key search terms cytochrome P450, drug—drug interaction, inhibition constant, and Ki. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and information deemed relevant was included for this review. DATA SYNTHESIS: The cytochrome P450 isoenzymes factor prominently in the explanation of numerous DDIs. Although the regulation of these enzymes by one drug can affect the pharmacokinetics of other drugs, the consequences may not necessarily be significant either in terms of pharmacokinetic or clinical outcomes. Yet, many DDI monographs originate as unconfirmed case reports that implicate the influence of one drug on the CYP-mediated metabolism of another, and these often uncorroborated mechanisms can eventually become regarded as dogma. One consequence of this process is the overprediction of potentially important DDIs. The pharmaceutical industry, Food and Drug Administration, and pharmaceutical scientists have developed a strategy for predicting the significance of inhibitory DDIs at the earliest possible stages of drug development based on a new chemical entity's Ki value, determined in vitro. CONCLUSIONS: We suggest that the use of Ki values of drugs purported to behave as CYP inhibitors be incorporated in the assessment of case reports that ascribe DDIs to inhibition of metabolism of one drug by another.

scholarly journals Fecal Microbiota Transplantation As a Therapeutic Option for Graft-Versus-Host-Disease: A Systematic Review and Future Directions

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4869-4869
Author(s):  
Hafiz muhammad Aslam ◽  
Sindhusha Veeraballi ◽  
Shahrukh K. Hashmi
Keyword(s):  
Graft Versus Host Disease ◽  
Clinical Studies ◽  
Case Reports ◽  
Therapeutic Option ◽  
Systemic Review ◽  
Fecal Matter ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction: In recent years, there has been an expanding focus on interplay between intestinal microbiotal diversity and outcome of acute graft versus host disease(GVHD) in hematopoietic stem cell transplantation (HCT) recipients. One of the compelling intervention to maintain healthy gut microbiota for better outcome of GVHD in HCT recipients is Fecal microbial transplantation(FMT). Several non randomized small clinical studies and case reports on the efficacy and safety of FMT were reported so far. However, the ultimate role of FMT as a therapeutic option to treat GVHD is yet to be determined due to lack of randomised, large scale, statistically significant studies. Here in, we report a systemic review of literature available so far in an effort to establish a definite role of FMT. Methodology: A systemic literature search was conducted using various electronic databases. The case reports, case series and clinical studies related to FMT were used as a therapeutic or preventative modality specifically for GVHD are included. Results: Upon pooling of data, 87 patients from 6 studies and 5 case reports were included in the study in which complete remission(CR) occured in 43.7% and partial remission(PR) occured in 20.7% patients which is equivalent to 64.4% overall response rate in treating GVHD. Furthermore, out of all the species in fecal matter, clostridium was found to be the most valuable species in decreasing the rates of GVHD re-occurrence. Only a limited number of patients had treatment-related mortality (TRM) from GVHD while few showed mild GI-related (abdominal pain/distention, nausea, regurgitation) and non-GI adverse reactions including infections, anemia, thrombocytopenia, paroxysmal, and atrial fibrillation. We emphasize that the most of the patients did not have any major complications after FMT. Conclusion: We conclude that the FMT is a safe and effective strategy for the management of GVHD based on our study. The establishment of gut diversity along with the patient's intrinsic factors like fucosyltransferase 2 (FUT2) secretor status and baseline gut microbial diversity play a major role in the success of FMT. Given the restricted size and absence of randomized data, one cannot portray FMT as a standard of care yet, however, the low or absent toxicity along with improvement in survival justifies this modality to be tested in a randomized fashion. We strongly encourage the transplant community to enroll patients in innovative trials utilizing FMT, as this may be a one of the safest strategies for both prevention and treatment of GVHD Disclosures No relevant conflicts of interest to declare.

scholarly journals Oxidative Stress in Graves Disease and Graves Orbitopathy

2020 ◽  
Vol 9 (Suppl. 1) ◽  
pp. 40-50
Author(s):  
Giulia Lanzolla ◽  
Claudio Marcocci ◽  
Michele Marinò
Keyword(s):  
Oxidative Stress ◽  
Clinical Studies ◽  
Therapeutic Option ◽  
Protective Role ◽  
Beneficial Effects ◽  
Antioxidant Agents ◽  
Graves Orbitopathy

Oxidative stress is involved in the pathogenesis of Graves hyperthyroidism (GH) and Graves orbitopathy (GO) and an antioxidant approach has been proposed for both. In GH, a disbalance of the cell redox state is associated with thyroid hyperfunction and antithyroid medications may reduce oxidative stress. Tissue hypoxia participates in the pathogenesis of GO, and oxygen free radicals are involved in the typical changes of orbital tissues as reported by in vitro and clinical studies. Antioxidant agents, especially selenium, have been proposed as a therapeutic option for GH and GO. A clinical study regarding the use of selenium in mild GO has provided evidence for a beneficial effect in the short term, even though its beneficial effects in the long term are still to be investigated. In addition to selenium, a protective role of other antioxidant agents, i.e., quercetin, enalapril, vitamin C, <i>N</i>-acetyl-L-cysteine and melatonin has been suggested by in vitro studies, although clinical studies are lacking. Here, we review the role of oxidative stress and antioxidant agents in GH and GO.

Prophylaxis of HIV Infection following Occupational Exposure

1993 ◽  
Vol 27 (10) ◽  
pp. 1243-1256 ◽  
Author(s):  
Douglas N. Fish
Keyword(s):  
Occupational Exposure ◽  
Hiv Infection ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Inoculum Size ◽  
Current Data ◽  
Human Studies ◽  
Retroviral Infection

OBJECTIVE: To review the risk of HIV infection following occupational exposure, the theoretical basis for chemoprophylaxis, investigative experience with chemoprophylaxis in animals and humans, and the economic aspects of postexposure chemoprophylaxis. DATA SOURCES: English-language articles and conference proceedings pertaining to the risk of occupational HIV infection and to postexposure chemoprophylaxis. STUDY SELECTION: Studies evaluating chemoprophylaxis of HIV infection following occupational exposure were selected for review. Abstracts reporting ongoing clinical trials were also included. DATA EXTRACTION: In vitro studies are discussed to provide the immunologic rationale for chemoprophylaxis. Animal studies examining the efficacy of chemoprophylaxis in preventing non-HIV retroviral infection are reviewed, and their applicability to human HIV infection is critically evaluated. Human studies and case reports describing attempts at chemoprophylaxis of HIV infection following occupational exposure are discussed. DATA SYNTHESIS: Chemoprophylaxis of HIV infection following occupational exposure has focused on the use of zidovudine (ZDV) because it was previously the only antiretroviral agent approved for treating HIV infection. Animal models of retroviral infection provide conflicting data regarding the efficacy of ZDV chemoprophylaxis, and there are important questions about the applicability of animal data to human HIV infection because of differences in natural histories of non-HIV retroviral infections, inoculum size, dosing of ZDV, and routes of infection. Human surveillance studies are thus far inadequate to determine the efficacy of ZDV prophylaxis because of the very low HIV seroconversion rates following occupational exposure. ZDV is well tolerated during short-term administration in people without HIV infection, but long-term safety is unknown. In addition, the true cost-benefit ratio of ZDV chemoprophylaxis is uncertain. CONCLUSIONS: Current data from in vitro, animal, and human studies are inadequate to define the appropriate role of ZDV in preventing HIV infection following occupational exposure. Limited toxicity data and the high cost of treatment must be weighed against the theoretical benefits of ZDV use in this setting. The decision to employ ZDV for postexposure prophylaxis must ultimately be based on existing institutional policies, the attitude of the responsible physician regarding such practice, and/or the desires of the exposed healthcare worker after being properly informed of potential risks and benefits.

scholarly journals Pharmacokinetic Properties of Clarithromycin: A Comparison with Erythromycin and Azithromycin

1993 ◽  
Vol 4 (3) ◽  
pp. 148-152 ◽  
Author(s):  
Marc LeBel
Keyword(s):  
Therapeutic Option ◽  
Data Extraction ◽  
Pharmacokinetic Profile ◽  
Data Synthesis ◽  
The Past ◽  
Study Selection ◽  
Pharmacokinetic Properties ◽  
New Compounds ◽  
Antibacterial Spectrum

Objective: To compare the pharmacokinetic properties of two new macrolide antibiotics, clarithromycin and azithromycin, with those of the prototype macrolide, erythromycin.Data Sources: Primarily peer review journals were searched for papers describing the pharmacokinetics of these new macrolides.Study Selection: Fifteen in vitro and clinical studies of clarithromycin and azithromycin and one clinical abstract on clarithromycin from the past four years were selected for review.Data Extraction: Data relevant to the pharmacokinetic characteristics of clarithromycin, azithromycin and, to a lesser extent, erythromycin were selected for presentation in this comparison.Data Synthesis: By reviewing the available studies, it was possible to construct pharmacokinetic profiles of the new compounds, and to compare them with each other and with erythromycin.Conclusions: Both clarithromycin and azithromycin have been shown to have an antibacterial spectrum and pharmacokinetic profile superior to that of erythromycin. The differences between the new compounds, however, may not be that significant. Each is likely to become a first-line therapeutic option in specific instances, which will become better delineated as clinical research on these new macrolides continues.

Sugar Paste for Treatment of Decubital Ulcers

1996 ◽  
Vol 12 (6) ◽  
pp. 289-290 ◽  
Author(s):  
Laura Tuneu Valls ◽  
Magdalena Trullás Altisen ◽  
Ramón Plá Poblador ◽  
Angels Ciurán Alvarez ◽  
Rosa Garriga Biosca
Keyword(s):  
English Language ◽  
Case Reports ◽  
Low Cost ◽  
Data Extraction ◽  
Data Synthesis ◽  
Length Of Treatment ◽  
Study Selection ◽  
Wide Variability

Objective: To review the use of sugar paste in the treatment of decubital ulcers. Data Sources: A MEDLINE, IDIS, and current journal search of English-language articles published between 1978 and 1993 on sugar paste in the treatment of ulcers. Study Selection: Case reports, cohort, epidemiologic, in vivo, and in vitro studies were evaluated. Data Extraction: Reports using granulated sugar or derivatives in the treatment of refractory cutaneous ulcers were evaluated. Data Synthesis: All the studies show that sugar paste treatment has satisfactorily resolved decubital ulcers, although a wide variability in treatment length has been seen. Considering the likely mechanisms of action for sugar paste, this wide variability may be a result of dressing frequency. In other words, for sugar paste to be most effective it has to be applied in such a way that a continuous optimal sugar concentration in the ulcer is maintained. To achieve this, dressing frequency should not be standardized, but individualized according to ulcer type, depth, and exudate, as well as patient healing capacity. Healing could probably have been achieved earlier if dressing had been individualized. Besides effectiveness and low cost, sugar paste is also safe, with few adverse events associated with its use. Conclusions: In spite of difficulties in evaluating the use of sugar paste in treatment of decubital ulcers, it has been shown to be an effective therapy for this disorder. However, we recommend that length of treatment be individualized for each patient.

scholarly journals Review of Ceftazidime-Avibactam, Meropenem-Vaborbactam, and Imipenem/Cilastatin-Relebactam to Target Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales

2020 ◽  
Vol 36 (5) ◽  
pp. 202-210
Author(s):  
Dillon A. Hayden ◽  
Bryan P. White ◽  
Kiya K. Bennett
Keyword(s):  
Klebsiella Pneumoniae ◽  
English Language ◽  
Antimicrobial Agents ◽  
Product Information ◽  
Data Extraction ◽  
Global Scale ◽  
Current Data ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Ovid Medline ◽  
Study Selection

Objective: To provide a review of 3 novel antimicrobial agents—ceftazidime-avibactam, meropenem-vaborbactam, and imipenem/cilastatin-relebactam—regarding treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC). Data Sources: A literature search of PubMed and OVID (MEDLINE) was performed up to March 2020 using the following search terms: Vabomere, meropenem-vaborbactam, vaborbactam, RPX7009, Klebsiella pneumoniae carbapenemase, KPC, carbapenem-resistant Enterobacteriaceae, CRE, relebactam, imipenem-relebactam, MK-7655, ceftazidime-avibactam. Abstracts from conferences, article bibliographies, and product information were also reviewed. Study Selection and Data Extraction: Articles were first screened by English language, then title, then abstract, and finally by review of the full article. Fifty-five clinical and preclinical studies were included. Data Synthesis: These 3 novel β-lactam/β-lactamase inhibitor combinations have shown considerable improvement in safety and efficacy as compared with traditional polymyxin-based combination therapy for the treatment of KPC infections. While meropenem-vaborbactam has not shown improved activity against Pseudomonas aeruginosa, it has shown decreased rates of resistance to KPC versus ceftazidime-avibactam. Conclusions: With increasing incidence of KPC infections on a global scale, pharmacists should be aware of the notable similarities and differences between these 3 agents, and the current data supporting their use. Pharmacists may want to consider meropenem-vaborbactam over ceftazidime-avibactam for KPC infections due to decreased likelihood of resistance.

LInezolid for the Treatment of Nocardia spp. Infections

2007 ◽  
Vol 41 (10) ◽  
pp. 1694-1699 ◽  
Author(s):  
Tomasz Z Jodlowski ◽  
Igor Melnychuk ◽  
John Conry
Keyword(s):  
Case Reports ◽  
Data Extraction ◽  
Central Nervous System Involvement ◽  
Case Series ◽  
Published Data ◽  
Data Synthesis ◽  
Study Selection ◽  
Disseminated Disease

Objective: To review the available evidence regarding the use of linezolid for the treatment of Nocardia spp. infections. Data Sources: Data were identified through a search of MEDLINE (1966-May 2007), American Search Premier (1975-May 2007), International Pharmaceutical Abstracts (1960-2007), Science Citation Index Expanded (1996-2007), and Cochrane Databases (publications archived until May 2007) using the terms linezolid and Nocardia. Study Selection and Data Extraction: Prospective and retrospective studies, case reports, case series, and in vitro studies were eligible for inclusion if they used linezolid for nocardiosis regardless of site of infection and outcome. Data Synthesis: We identified 11 published cases of linezolid use for Nocardia spp. infections. The predominant species isolated were N. asteroides (n=4; 36%) and N. farcinica (n= 3; 27%). Nocardiosis with central nervous system involvement (n= 7; 64%) or disseminated disease (n= 4; 36%) were most common. The main reason for discontinuation of previous antimicrobials was most often related to adverse effects (n= 5; 45%), followed by clinical failure (n = 3; 27%). Linezolid was associated with cure or improvement in all cases (n =11; 100%). However, the majority of patients developed serious complications that may have led to premature discontinuation of therapy with linezolid, including myelosuppression (n = 5; 45%) or possible/confirmed peripheral neuropathy (n = 2; 18%). Conclusions: The limited published data suggest that linezolid appears to be an effective alternative to trimethoprim/sulfamethoxazole for the treatment of nocardiosis. Unfortunately, the high cost and potentially serious long-term toxicities of linezolid appear to limit its use and relegate it to salvage therapy alone or in combination with other antimicrobials.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea

2017 ◽  
Vol 52 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Rebecca M. Hoover ◽  
John Erramouspe
Keyword(s):  
English Language ◽  
Human Subjects ◽  
Data Extraction ◽  
Drug Approval ◽  
Current Data ◽  
Patient Response ◽  
Study Selection ◽  
Cochrane Database ◽  
Drug Approval Process ◽  
Individual Patient Response

Objective: To review and summarize topical oxymetazoline’s pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. Data Sources: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. Study Selection and Data Extraction: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. Data Synthesis: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. Conclusion: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

Drug-Induced Restless Legs Syndrome

2018 ◽  
Vol 52 (7) ◽  
pp. 662-672 ◽  
Author(s):  
Edna Patatanian ◽  
Melanie K. Claborn
Keyword(s):  
Restless Legs Syndrome ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Case Series ◽  
Predisposing Factors ◽  
Drug Induced ◽  
Restless Legs ◽  
Drug Classes ◽  
Study Selection

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS). Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

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