Antibiotic Lock Technique: A Review of the Literature

2005 ◽  
Vol 39 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Marisel Segarra-Newnham ◽  
Ellen M Martin-Cooper
Keyword(s):  
Data Extraction ◽  
Success Rates ◽  
Coagulase Negative Staphylococci ◽  
Systemic Complications ◽  
Study Selection ◽  
Gram Negative Bacteremia ◽  
Antibiotic Lock ◽  
Therapy Success ◽  
Antibiotic Lock Technique

OBJECTIVE: To review the literature on the use of the antibiotic lock technique (ALT) as a treatment option for patients with highly needed catheters. DATA SOURCES: MEDLINE and International Pharmaceutical Abstracts were searched (1980–August 2004). Search terms included antibiotic lock, catheter infection, and topical treatment. STUDY SELECTION AND DATA EXTRACTION: Articles describing use of ALT in the treatment of catheter infections in humans and studies evaluating in vitro stability of antibiotics were included. DATA SYNTHESIS: ALT has been used in patients with highly needed catheters, usually for parenteral nutrition, cancer chemotherapy, or dialysis. Catheters are considered highly needed when removal is not feasible or desirable due to lack of alternative injection sites for required therapy. Success rates in saving the infected catheter have been variable and may depend on the infecting organism. In addition, there are conflicting data in terms of compatibility of antibiotics with heparin solutions. CONCLUSIONS: Consensus appears to be that the ALT can be tried for patients with highly needed catheters when infection with coagulase-negative staphylococci is documented and no systemic signs of sepsis, such as hypotension, are evident. Most of these patients are likely to need systemic therapy as well. Infection of the catheter associated with systemic gram-negative bacteremia or fungemia will most likely require removal of the catheter to prevent systemic complications. Additional research with the ALT is warranted given unanswered questions.

Meropenem/Vaborbactam, the First Carbapenem/β-Lactamase Inhibitor Combination

2018 ◽  
Vol 52 (8) ◽  
pp. 769-779 ◽  
Author(s):  
Jonathan C. Cho ◽  
Monika T. Zmarlicka ◽  
Kristy M. Shaeer ◽  
Joe Pardo
Keyword(s):  
English Language ◽  
Clinical Success ◽  
Data Extraction ◽  
Phase Iii ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Preclinical Phase ◽  
Study Selection ◽  
Tract Infections ◽  
Lactamase Inhibitor

Objective: To review the pharmacology, spectrum of activity, pharmacokinetics, pharmacodynamics, safety, efficacy, administration, and considerations for clinical use of meropenem/vaborbactam (M/V). Data Sources: A literature search using PubMed and clinicaltrials.gov (June 2013 to December 2017) was conducted using the search terms meropenem, vaborbactam, RPX7009, biapenem, RPX2003, and carbavance. References from relevant articles and conference abstracts were also reviewed. Study Selection and Data Extraction: Preclinical, phase I studies, and phase III studies written in the English language were evaluated. Data Synthesis: M/V is a novel carbapenem/β-lactamase inhibitor antimicrobial with in vitro activity against nearly 99% of Klebsiella pneumoniae carbapenemase–producing Enterobacteriaceae. M/V is approved for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis. In a phase III cUTI trial (TANGO I), 98.4% of patients treated with M/V experienced overall clinical success compared with 94% of patients treated with piperacillin/tazobactam (95% CI = 0.7 to 9.1). When compared with best available therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections in TANGO II, patients receiving M/V were more likely to achieve clinical cure at both the end of therapy (64.3% vs 33.3%, P = 0.04) as well as at the test of cure (57.1% vs 26.7%, P = 0.04). The most common adverse effects associated with M/V were headache, infusion-site reactions, and diarrhea. Conclusion: M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.

scholarly journals Comparative Efficacies of Quinupristin-Dalfopristin, Linezolid, Vancomycin, and Ciprofloxacin in Treatment, Using the Antibiotic-Lock Technique, of Experimental Catheter-Related Infection Due to Staphylococcus aureus

2005 ◽  
Vol 49 (10) ◽  
pp. 4042-4045 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Fiorenza Orlando ◽  
Federico Mocchegiani ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Venous Catheter ◽  
Blood Cultures ◽  
Adherent Cell ◽  
Minimal Bactericidal Concentration ◽  
Biofilm Model ◽  
Isotonic Sodium Chloride ◽  
Antibiotic Lock ◽  
Antibiotic Lock Technique

ABSTRACT We performed in vitro studies to elucidate the bactericidal activity of the antibiotics in an adherent-cell biofilm model. Efficacy studies were performed in a staphylococcal central venous catheter (CVC) infection rat model. Silastic catheters were implanted into the superior cava. Via the CVC the rats were challenged with 1.0 × 106 CFU of a live Staphylococcus aureus strain. Twenty-four hours later, the antibiotic-lock technique was started. All animals were randomized to receive daily isotonic sodium chloride solution, quinupristin-dalfopristin (Q/D), linezolid, vancomycin, or ciprofloxacin at the minimal bactericidal concentration (MBC) and at 1,024 μg/ml in a volume of 0.1 ml that filled the CVC. The main outcome measures were MICs and MBCs for both planktonic and adherent cells, quantitative culture of the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. The killing activities of all antibiotics against the adherent bacteria were at least fourfold lower than those against freely growing cells, with the exception of Q/D, which showed comparable activities against both adherent and planktonic organisms. Overall, Q/D at 1,024 μg/ml produced the greatest reduction in the number of cells recovered from the catheters, while at the same concentration, Q/D and vancomycin demonstrated higher activities than ciprofloxacin or linezolid in reducing the number of organisms recovered from the blood cultures. This study points out that treatment outcome of device-related infections cannot be predicted by the results of a standard susceptibility test such as the MIC. Our findings suggest that the clinically used antibiotics cannot eradicate the CVC infection through the antibiotic-lock technique, even at a concentration of 1,024 μg/ml.

Omadacycline: A New Tetracycline Antibiotic

2018 ◽  
Vol 53 (5) ◽  
pp. 486-500 ◽  
Author(s):  
John A. Dougherty ◽  
Allana J. Sucher ◽  
Elias B. Chahine ◽  
Katherine C. Shihadeh
Keyword(s):  
Data Extraction ◽  
Phase 1 ◽  
Common Adverse Effect ◽  
Tetracycline Antibiotic ◽  
Search Terms ◽  
Study Selection ◽  
Alternative Treatment Option ◽  
Wide Range ◽  
Resistant Strains

Objective: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of omadacycline, a new tetracycline antibiotic. Data Sources: A literature search through PubMed, Google Scholar, and clinicaltrials.gov was conducted (2008 to October 2018) using the search terms omadacycline and PTK-0796. Abstracts presented at recent conferences, prescribing information and information from the FDA and the manufacturer’s website were reviewed. Study Selection and Data Extraction: Preclinical data and published phase 1, 2, and 3 studies were evaluated. Data Synthesis: Omadacycline displays in vitro activity against a wide range of bacteria. Clinical trials have shown that omadacycline is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg intravenously (IV) once or 100 mg IV twice or 450 mg orally for two days is recommended followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No dosage adjustment is needed in patients with renal or hepatic impairment. Omadacycline is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Relevance to Patient Care and Clinical Practice: Omadacycline is active against staphylococci, including methicillin-resistant strains, and streptococci, including tetracycline-resistant strains, as well as atypical bacteria. Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP. Conclusion: Omadacycline is an alternative treatment option for ABSSSI and CABP.

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.

Brexpiprazole

2016 ◽  
Vol 51 (4) ◽  
pp. 315-322 ◽  
Author(s):  
Marija Markovic ◽  
Alyssa Gallipani ◽  
Krina H. Patel ◽  
Megan Maroney
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Safety Data ◽  
Clinical Trial Data ◽  
Primary Therapy ◽  
Phase 3 ◽  
Good Tolerability ◽  
Study Selection ◽  
Animal Data

Objective: To review the pharmacology and clinical data for brexpiprazole in schizophrenia and major depressive disorder (MDD). Data Sources: An English-language literature search using PubMed and MEDLINE was performed using the term brexpiprazole. All articles containing human clinical trial data published up to September 2016 were evaluated for inclusion as well as information from the manufacturer’s product labeling. Study Selection/Data Extraction: Phase 3 trials for brexpiprazole were evaluated. Key in vitro and animal data were incorporated into the pharmacology and pharmacokinetic sections where appropriate. Data Synthesis: Four phase 3 trials have evaluated the use of brexpiprazole as a primary therapy for schizophrenia or as an antidepressant adjunct for MDD. For its schizophrenia indication, brexpiprazole was studied in 2 placebo-controlled trials of approximately 1300 patients, with 4 mg of brexpiprazole consistently showing superiority over placebo. For MDD, brexpiprazole was compared with placebo as an adjunct to antidepressants in approximately 1000 patients who had failed trials of 1 to 3 prior antidepressants. The 2-mg and 3-mg dosages of brexpiprazole showed consistent superiority over placebo in the MDD trials. Common treatment emergent adverse effects included akathisia and weight gain. Conclusions: Brexpiprazole showed efficacy for the treatment of schizophrenia in the range of 2 to 4 mg/d and as an adjunct to antidepressant therapy in MDD when dosed at 2 to 3 mg/d. Advantages of this drug include once-daily dosing, good tolerability, and lack of effect on sexual function. Disadvantages include the lack of long-term safety data and potentially high cost.

Maximizing Pharmacodynamics with High-Dose Levofloxacin

2005 ◽  
Vol 40 (9) ◽  
pp. 777-788 ◽  
Author(s):  
Kurt A. Wargo ◽  
Nichole A. Wargo ◽  
Edward H. Eiland
Keyword(s):  
Adverse Effects ◽  
Data Extraction ◽  
Community Acquired Pneumonia ◽  
High Dose ◽  
Data Synthesis ◽  
Search Terms ◽  
Short Course ◽  
Study Selection ◽  
Dosage Formulation

Objective To review published literature of levofloxacin 750 mg for the treatment of community-acquired pneumonia (CAP), nosocomial-acquired pneumonia (NAP), and skin and skin-structure infections (SSSI) focusing on microbiology, pharmacokinetic, and pharmacodynamic parameters. Data Sources MEDLINE was searched for clinical trials and review articles (1966 to September 2004). Also included were data from the manufacturer. Search terms utilized were levofloxacin, pneumonia, skin infections, adverse effects, pharmacokinetics, pharmacodynamics, and resistance. Study Selection and Data Extraction All articles and product labeling regarding levofloxacin for the treatment of CAP, NAP, and SSSI were included for review. Data Synthesis Compared with the other currently marketed fluoroquinolones, levofloxacin demonstrates similar in vitro activity to a number of commonly identified microorganisms. Levofloxacin 750 mg has shown equivalency to various non-fluoroquinolone regimens for the treatment of NAP and SSSI. Furthermore, a short, 5-day course of levofloxacin 750 mg was similar in efficacy to a longer, 10-day course of levofloxacin 500 mg for the treatment of CAP. Adverse events associated with levofloxacin therapy are dose independent; therefore, the adverse effects seen with high-dose levofloxacin are comparable to lower doses. Conclusions The levofloxacin 750 mg dosage formulation is a logical option when evaluating the antimicrobial armamentarium commonly utilized for the empiric treatment of CAP, NAP, and SSSI. Pharmacodynamic parameters are optimized and resistance is minimized when high-dose, short-course therapy is implemented.

Clarithromycin: Review of a New Macrolide Antibiotic with Improved Microbiologic Spectrum and Favorable Pharmacokinetic and Adverse Effect Profiles

1992 ◽  
Vol 26 (9) ◽  
pp. 1099-1108 ◽  
Author(s):  
Marc G. Sturgill ◽  
Robert P. Rapp
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Antimicrobial Agents ◽  
Macrolide Antibiotic ◽  
Data Extraction ◽  
Specific Information ◽  
Study Selection ◽  
Stated Purpose

OBJECTIVE: To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity. DATA IDENTIFICATION: An English-language literature search employing MEDLINE (1987–91), Index Medicus (1987–91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles. STUDY SELECTION: Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. DATA EXTRACTION: Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity. RESULTS OF DATA ANALYSIS: A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium aviumintracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections. CONCLUSIONS: Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.

scholarly journals Delafloxacin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

2019 ◽  
Vol 35 (3) ◽  
pp. 110-118
Author(s):  
Young Ran Lee ◽  
Caitlin Elizabeth Burton ◽  
Kolton Rucks Bevel
Keyword(s):  
Treatment Option ◽  
English Language ◽  
Data Extraction ◽  
Additional Treatment ◽  
Effective Treatment Option ◽  
Skin Structure ◽  
Patient Morbidity ◽  
Study Selection ◽  
Pubmed Search

Objective: To review the microbiological activity, safety, and efficacy of the new fluoroquinolone delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Data Sources: A PubMed search from 1945 to September 2018 was done using the terms delafloxacin, acute bacterial skin and skin structure infections, skin and soft tissue infections, and fluoroquinolone. Additional sources include the Food and Drug Administration website, ClinicalTrials.gov, and the Melinta Therapeutics website. Study Selection and Data Extraction: The literature search was limited to those published in the English language and included in vitro and human studies that evaluated microbiological coverage, pharmacokinetics, pharmacodynamics, safety, and/or efficacy. Data Synthesis: Delafloxacin is a new fluoroquinolone with a unique structure for its class that covers both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. This new antibiotic has demonstrated noninferiority to vancomycin plus aztreonam for the treatment of ABSSSIs in both an intravenous-only regimen and an intravenous to an oral regimen. Relevance to Patient Care and Clinical Practice: ABSSSIs are infections that are most often caused by Staphylococcus and represent one of the most common types of hospital infections. MRSA represents about half of all staphylococcal skin infections, and along with gram-negative infections, increase the rates of patient morbidity and health care costs. Delafloxacin is an additional treatment option that covers both of these types of microorganisms. Conclusions: Delafloxacin is a safe and effective treatment option for ABSSSIs, particularly in those with polymicrobial infections and those with MRSA.

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.

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