DOCSLIB.ORG

"Hot Off the Patients“ What's New with Bugs & Drugs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
10/1/2019 "Hot Off the Patients“ What's New with Bugs & Drugs David T. Bearden, Pharm.D., FIDP, FCCP Clinical Professor, Department of Pharmacy Practice Associate Dean for Academic Integration and Clinical Advancement Clinical Assistant Director, Department of Pharmacy Services Oregon State University/Oregon Health & Science University College of Pharmacy 1 New Drugs – quick hits DISCLAIMER – “New systemic antibacterials that I like.” • Approved in the last 5 years • Excluding • TB • Topical • Anti-virals 2 1 10/1/2019 2/3 rule: Two (plus 1) “X”s and 1 (plus 2) “Z” 2015 2018 ceftazidime-avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic- area/25/infections-and-infectious-diseases 3 Resistant Gram-negative Pathogens - Added β-lactamases 2015 2018 Ceftazidime/avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) 4 2 10/1/2019 Bad (East Coast) GNRs ESBLs KPCs • Extended spectrum β- • Klebsiella pneumoniae lactamases carbapenemases • Oregon E. coli 8.3% , US 13.4% • Oregon K. pneumonia 6.6%, US 20% • Oregon 0%, national 8.7% • Resistance to most • Generally provide resistance to cephalosporins, penicillins, and all β-lactams, including β- aztreonam lactamase inhibitors combinations • Carbapenems are generally resistant to ESBL hydrolysis https://gis.cdc.gov/grasp/PSA/MapView.html 5 Quick Drug Facts – IV only, ESBLs, KPCs Cephalosporin/β-lactamase inhibitor Carbapenem/β-lactamase inhibitor • Ceftazidime/avibactam • Meropenem/vaborbactam • Improved activity against • Imipenem/relebactam • Pseudomonas sp. • Improved activity against • Carbapenem-resistant Enterobactericeae (CRE) • ESBLs • KPCs • AmpC β-lactamases • Pseudomonas (*imi/relebactam only*) https://commons.wikimedia.org/w/index.php?curid=40665787 Pharmacotherapy. 2015 Aug; 35(8): 755–770. Drugs. 2018 Jan;78(1):65-98. 6 3 10/1/2019 Resistant Gram-negative Pathogens - New Tetracyclines 2015 2018 ceftazidime-avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) 7 Quick Drug Facts – restores tetracycline spectrum Omadacycline (IV and PO) Eravacycline (IV only) • Targeted CAP and SSTI • Targeted intra-ab organisms pathogens • MRSA, VRE • MRSA, S. pneumoniae, VRE • MDR GNR – CRE & ESBLs • H. flu, Moraxella, ESBL/CRE • No Pseudomonas! • Atypical respiratory pathogens • True anaerobes Drugs. 2016 Apr;76(5):567-88 Clin Infect Dis. 2019 Aug 1;69(Supplement_1):S1-S5 8 4 10/1/2019 New fluoroquinolone 2015 2018 ceftazidime-avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic- area/25/infections-and-infectious-diseases 9 Quick Drug Facts – Delafloxacin • IV & PO • “Usual” FQ activity, plus… • Covers MRSA! (though concerns about future resistance) • Pseudomonas • Anaerobes • Typical FQ warnings Infect Dis Ther. 2018 Jun; 7(2): 197–217. 10 5 10/1/2019 Fluoroquinolones – adverse reactions • Common* • Gastrointestinal • Nausea • Central nervous system • HA, dizziness, insomnia The Pharmaceutical Journal 22 JAN 2015 * Side effects led FDA 2016 to recommend against FQ use in uncomplicated UTI, sinusitis, and bronchitis 11 Fluoroquinolones – adverse reactions • Less common* • Cartilage toxicity: AVOID children/pregnancy • CNS: confusion, seizures, hallucinations, delirium* • Severe hypoglycemia* • Peripheral neuropathy • Prolonged cardiac QT interval • Increased with other similar drugs *2018 FDA Black Box Warnings 12 6 10/1/2019 NO FQ’s? • Look for alternatives • Search deeper in guidelines • Newer guidelines will start to tackle these issues • Presently, push listed alternatives (sometimes less data) 13 New aminoglycoside 2015 2018 ceftazidime-avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) 14 7 10/1/2019 Quick Drug Facts – nudged activity aminoglycoside • Plazomicin • Currently approved for complicated UTI • Typical aminoglycoside coverage – GNR focus! • Added activity for Enterobacteriacea w/ AG resistance • May have benefits for systemic infections with carbapenem resistant isolates! Drugs. 2019 Feb;79(3):243-269. 15 UTI - epidemiology of E. coli resistance NW Regional HMO, primary care • Ampicillin ~66% • Ciprofloxacin ~94% • Nitrofurantoin ~97% • TMP / SMX ~85% McGregor JC, et al. BMC Fam Pract. 2013 Feb 22;14:25 16 8 10/1/2019 New imidazole (think metronidazole) 2015 2018 ceftazidime-avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) 17 Bacterial Vaginosis Therapy Current CDC Recommendations Secnidazole “Recommended” • 2g PO granules X 1 dose • Metronidazole 500 mg PO BID for • 17h t 1/2 7 days • No disulfiram-like reaction • Topical – metronidazole or clindamycin “Alternatives” • Tinidazole 2g PO QD for 2 days • Tinidazole 1g PO QD for 5 days • Clindamycin PO or topical MMWR Recomm Rep 2015;64(No. RR-3): 1-137. 18 9 10/1/2019 NEW ENTITY! - pleuromutilin 2015 2018 ceftazidime-avibactam (Avycaz) plazomicin (Zemdri) eravacycline (Xerava) 2017 omadacycline (Nuzyra) delafloxacin (Baxdela) mero/vaborbactam (Vabomere) 2019 secnidazole (Solosec) imi/relebactam (Recarbrio) lefamulin (Xenleta) 19 Drug Facts – lefamulin (IV & PO) • First pleuromutilin – 50S ribosomal protein synthesis inhibitor • Spectrum of Activity • GPC – including MRSA, S. pneumonia • GNR – H. flu, Moraxella catarrhalis • Atypical respiratory pathogens • Targeted for community-acquired pneumonia (maybe SSTI) Pharmacotherapy. 2018 Sep;38(9):935-946 20 10 10/1/2019 "Hot Off the Patients“ What's New with Bugs & Drugs David T. Bearden, Pharm.D., FIDP, FCCP Clinical Professor, Department of Pharmacy Practice Associate Dean for Academic Integration and Clinical Advancement Clinical Assistant Director, Department of Pharmacy Services Oregon State University/Oregon Health & Science University College of Pharmacy 21 11 10/1/2019 Updates in Diabetes Management: 2019 Andrew Bzowyckyj, PharmD, BCPS, CDE Associate Professor Pacific University Oregon School of Pharmacy [email protected] 1 Session Objectives • Summarize key updates to the American Diabetes Association Standards of Medical Care in Diabetes • Describe new agents approved and in the pipeline for type 1 and type 2 diabetes • Discuss factors to consider when adding these new medications for specific patient populations 2 1 10/1/2019 Session Outline: Top 10 Updates 1. Designing medication 6. New medication updates – Oral semaglutide regimens – SGLT inhibitors in type 1 2. SGLT-2 inhibitors in renal diabetes – New formulations of glucagon insufficiency 3. What’s the deal with 7. Continuous Glucose aspirin? Monitoring (CGM) 4. Blood pressure treatments 8. Use of language in diabetes 5. De-prescribing & care & education simplifying regimens in the 9. ADA Consensus Report on elderly Nutrition 10. Insulin price wars & resources 3 GUIDELINE UPDATES 4 2 10/1/2019 Diabetes Care 2019;42 (Suppl. 1):S90-S102. 5 1. Intensifying Injectable Therapies (Basal / GLP-1) Diabetes Care 2019;42 (Suppl. 1):S90-S102. 6 3 10/1/2019 1. Intensifying Injectable Therapies (Prandial Insulin) Diabetes Care 2019;42 (Suppl. 1):S90-S102. 7 1. Intensifying Injectable Therapies Diabetes Care 2019;42 (Suppl. 1):S90-S102. 8 4 10/1/2019 1. Considering oral & injectable combinations? Diabetes Care 2018;41(12):2669-701. 9 1. Considering oral & injectable combinations? Diabetes Care 2018;41(12):2669-701. 10 5 10/1/2019 2. SGLT-2 Inhibitors in Renal Insufficiency Use Not Studied in CV Drug Dosing Recommended Type 1 Indication 100-300mg QAM Canagliflozin eGFR 45-59: max 100 mg eGFR <45ml/min Yes Yes daily Dapagliflozin 5-10mg QAM eGFR <45ml/min Yes No Empagliflozin 10-25 mg QAM eGFR <45ml/min Yes Yes Ertugliflozin 5-15mg QAM eGFR <60ml/min No No UPDATE: Consider SGLT2i in people with eGFR ≥ 30 and particularly in those with >300 mg/g albuminuria to reduce risk of CKD progression, cardiovascular events, or both. (Level A) Diabetes Care 2019;42 (Suppl. 1):S124-8. 11 3. What’s the deal with aspirin? Secondary YES Prevention Primary Prevention NO (<50 years) Primary Consider if Not high CV risk Prevention recommended (50-69 years) and low GI risk Primary Prevention NO (70+ years) Diabetes Care 2019;42 (Suppl. 1):S113-4. 12 6 10/1/2019 4. What are we doing with blood pressure? Secondary 10-year ASCVD 10-year ASCVD Prevention risk > 15% risk < 15% • Less than • Less than • Less than 130/80 may be 130/80 may be 140/90 appropriate if it appropriate if it can be safely can be safely attained attained Diabetes Care 2019;42 (Suppl. 1):S104. 13 4. What are we doing with blood pressure? *ACEI or ARB suggested if UACR 30-299, and strongly recommended for UACR > 300 **Thiazide-like diuretic; long-acting agents shown to reduce
Load more

Recommended publications
  • Plazomicin Sulfate ASHP INJECTABLE DRUG INFORMATION
    1302 PLAZOMICIN SULFATE ASHP INJECTABLE DRUG INFORMATION Plazomicin Sulfate AHFS 8:12.02 Products Stability Plazomicin sulfate is available in a concentration equivalent Intact vials of plazomicin sulfate should be stored under refrig- to plazomicin base 50 mg/mL in 10-mL single-dose (preserva- eration at 2 to 8°C.3431 Plazomicin sulfate injection is a clear, tive-free) vials.3431 Each vial also contains sodium hydroxide colorless to yellow solution.3431 The manufacturer states that for pH adjustment and water for injection.3431 The appropriate the solution may become yellow, but that this change does not dose of plazomicin solution should be diluted in sodium chloride indicate a decrease in potency.3431 0.9% or Ringer’s injection, lactated to achieve a final volume of The manufacturer states that a solution of plazomicin diluted 3431 50 mL. for infusion in sodium chloride 0.9% or Ringer’s injection, pH lactated to concentrations of 2.5 to 45 mg/mL is stable for up to 24 hours at room temperature.3431 Adjusted to 6.5.3431 Trade Name(s) Zemdri Administration Plazomicin sulfate is administered by intravenous infusion over 30 minutes after dilution in sodium chloride 0.9% or Ringer’s injection, lactated.3431 Compatibility Information Solution Compatibility Plazomicin sulfate Test Soln Name Mfr Mfr Conc/L or % Remarks Ref C/I Ringer’s injection, lactated ACH 2.5 to 45 g Stable for 24 hr at room temperature 3431 C Sodium chloride 0.9% ACH 2.5 to 45 g Stable for 24 hr at room temperature 3431 C Y-Site Injection Compatibility (1:1 Mixture) Plazomicin
    [Show full text]
  • The Pharmacodynamics of Plazomicin and Amikacin Studied in an in Vitro
    P203 The pharmacodynamics of plazomicin and amikacin studied in an in vitro pharmacokinetic model Karen E Bowker 1, Alan R Noel 1, Marie A Attwood 1, Sharon G Tomaselli 1, Alasdair P MacGowan 1, Kevin Krause 2, Eileen Kim 2 BCARE, Department of Microbiology, North Bristol NHS Trust, Bristol, UK. 1 Achaogen Inc, South San Francisco, California, USA 2 [email protected] ASM MICROBE, New Orleans, 1-5th June, 2017 Introduction Results The AUC/MIC targets for amikacin administered 12hrly against E.coli (n=3) Aminoglycoside antibiotics have been a mainstay of antimicrobial Table 3: Individual and mean AUC/MIC targets for K.pneumoniae for were 12h static effect 16.1±10; -1 log drop 22.8±12.5; -2 log drop 32.4±12.4; chemotherapy for more than forty years yet the pre-clinical data on their plazomicin administered 12hrly pharmacokinetics-pharmacodynamics (PK-PD) is scarce. -3 log drop 59.3±11.9; 24h static effect 49.5±12.7; -1 log drop 55.7±14.8; -2 Endpoint strain AUC/MIC Published data points to AUC/MIC or Cmax/MIC as the dominant log drop 64.1±19.5; -3 log drop 73.3±25.3; 48hr static effect 78.6±35.9; -1 AKPN 1169 AKPN 1170 AKPN 1171 KP41965 KP41966 Mean ± STD pharmacodynamic index (PDI) with an AUC/MIC of 50-70 being associated log drop 81.0±36.6; -2 log drop 81.8±37.8; -3 log drop 84.2±38.9. 12h with 24h static effect for aerobic Gram-negative rods ( Enterobacteriaceae The AUC/MIC targets for plazomicin and amikacin against E.coli when 24h Static 15.2 66.1 40.7 37.6 17.2 35.3±20.7 -1 log drop 28.8 77.6 49.6 59.3 23.7 47.8±22.2 and Pseudomonas aeruginosa ).
    [Show full text]
  • ZEMDRI (Plazomicin) Injection, for Intravenous Use (Ml/Min) ZEMDRI B Dosing Interval Initial U.S
    HIGHLIGHTS OF PRESCRIBING INFORMATION Recommended initial dosage regimen for patients with renal These highlights do not include all the information needed to use impairment is shown in the table below. (2.3) ZEMDRI safely and effectively. See full prescribing Recommended information for ZEMDRI. Estimated CLcr a Dosage for ZEMDRI (plazomicin) injection, for intravenous use (mL/min) ZEMDRI b Dosing Interval Initial U.S. Approval: 2018 Greater than or equal to 60 15 mg/kg Every 24 hours WARNING: NEPHROTOXICITY, OTOTOXICITY, to less than 90 NEUROMUSCULAR BLOCKADE and FETAL HARM Greater than or equal to 30 10 mg/kg Every 24 hours See full prescribing information for complete boxed warning. to less than 60 Nephrotoxicity has been reported with ZEMDRI. The risk Greater than or equal to 15 10 mg/kg Every 48 hours of nephrotoxicity is greater in patients with impaired renal to less than 30 a CLcr estimated by the Cockcroft-Gault formula. (2.3) function, the elderly, and in those receiving concomitant b nephrotoxic medications. (5.1) Calculate dosage using Total Body Weight (TBW). For patients Ototoxicity, manifested as hearing loss, tinnitus, and/or with TBW greater than IBW by 25% or more, use adjusted body weight. (2.3) vertigo, has been reported with ZEMDRI. Symptoms of aminoglycoside associated ototoxicity may be irreversible See Full Prescribing Information for subsequent dosage and may not become evident until after completion of adjustment based on changes in renal function or Therapeutic therapy. (5.2) Drug Monitoring (TDM). (2.3, 2.4). Aminoglycosides have been associated with neuromuscular See Full Prescribing Information for instructions on preparation blockade.
    [Show full text]
  • Prospects for Circumventing Aminoglycoside Kinase Mediated Antibiotic Resistance
    REVIEW ARTICLE published: 25 June 2013 CELLULAR AND INFECTION MICROBIOLOGY doi: 10.3389/fcimb.2013.00022 Prospects for circumventing aminoglycoside kinase mediated antibiotic resistance Kun Shi 1, Shane J. Caldwell 1, Desiree H. Fong 1* and Albert M. Berghuis 1,2* 1 Groupe de Recherche Axé sur la Structure des Protéines, Department of Biochemistry, McGill University, Montreal, QC, Canada 2 Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada Edited by: Aminoglycosides are a class of antibiotics with a broad spectrum of antimicrobial activity. Marcelo Tolmasky, California state Unfortunately, resistance in clinical isolates is pervasive, rendering many aminoglycosides University Fullerton, USA ineffective. The most widely disseminated means of resistance to this class of antibiotics Reviewed by: is inactivation of the drug by aminoglycoside-modifying enzymes (AMEs). There are two Sylvie Garneau-Tsodikova, University of Michigan, USA principal strategies to overcoming the effects of AMEs. The first approach involves the Maria S. Ramirez, IMPaM design of novel aminoglycosides that can evade modification. Although this strategy has (UBA-CONICET), Argentina yielded a number of superior aminoglycoside variants, their efficacy cannot be sustained in *Correspondence: the long term. The second approach entails the development of molecules that interfere Desiree H. Fong, Groupe de with the mechanism of AMEs such that the activity of aminoglycosides is preserved. Recherche Axé sur la Structure des Protéines, Department of Although such a molecule has yet to enter clinical development, the search for AME Biochemistry, McGill University, inhibitors has been greatly facilitated by the wealth of structural information amassed 3649 Promenade Sir William Osler, in recent years.
    [Show full text]
  • E200069A Sihuan Pharm 1..2
    Hong Kong Exchanges and Clearing Limited and The Stock Exchange of Hong Kong Limited take no responsibility for the contents of this announcement, make no representation as to its accuracy or completeness and expressly disclaim any liability whatsoever for any loss howsoever arising from or in reliance upon the whole or any part of the contents of this announcement. Sihuan Pharmaceutical Holdings Group Ltd. 四環醫藥控股集團有限公司 (incorporated in Bermuda with limited liability) (Stock code: 0460) VOLUNTARY ANNOUNCEMENT ACQUISITION OF ALL INTERESTS AND INTELLECTUAL PROPERTY RIGHTS OF PLAZOMICIN, A NEW GENERATION OF AMINOGLYCOSIDE ANTIBIOTICS IN THE GREATER CHINA REGION The board of directors (the ‘‘Board’’) of Sihuan Pharmaceutical Holdings Group Ltd. (the ‘‘Company’’ or ‘‘Sihuan Pharmaceutical’’, together with its subsidiaries, the ‘‘Group’’) is pleased to announce that Xuanzhu (HK) Biopharmaceutical Limited (‘‘Xuanzhu’’), a wholly-owned subsidiary of the Group, acquired all interests and intellectual property rights of plazomicin, a new generation of aminoglycoside antibiotics, in the Greater China Region (including the People’s Republic of China (the ‘‘PRC’’), Hong Kong Special Administrative Region, Macau Special Administrative Region and Taiwan) from Achaogen, Inc. (‘‘Achaogen’’), a company incorporated in Delaware, the United States of America. Plazomicin is a new generation of semisynthetic aminoglycoside antibiotics developed by Achaogen. It produces antibacterial effect mainly through binding to bacterial 30S ribosomal subunits and is used to treat severe infections caused by multi-drug resistance (‘‘MDR’’) gram-negative bacteria and enterobacteriaceae, including the carbapenem-resistant enterobacteriaceae. In the PRC, MDR bacterial infections are mainly acquired in hospital and most of the infected individuals are immunocompromised due to various reasons.
    [Show full text]
  • Plazomicin for Complicated Urinary Tract Infection
    October Horizon Scanning Research & 2016 Intelligence Centre Plazomicin for complicated urinary tract infection NIHR HSRIC ID: 9787 Lay summary Serious infections caused by Gram-negative bacteria are becoming increasingly resistant to commonly prescribed antibiotics and are a serious global concern. If licensed, plazomicin will offer a treatment option for those patients who have a complicated urinary tract infection or acute pyelonephritis caused by multi-drug resistant Gram-negative bacteria, a group who currently have few effective and well tolerated therapies available. This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. Horizon Scanning Research & Intelligence Centre University of Birmingham [email protected] www.hsric.nihr.ac.uk @OfficialNHSC TARGET GROUP • Complicated urinary tract infection (cUTI), including acute pyelonephritis (AP); infection caused by resistant Gram-negative bacterial pathogens, including 3rd generation cephalosporin and carbapenem-resistant enterobacteriaceae (CRE) – first line, followed by appropriate, optional oral step down therapy. TECHNOLOGY DESCRIPTION Plazomicin (ACHN-490) is a next-generation broad-spectrum aminoglycoside antibiotic. Aminoglycosides kill bacteria by inhibiting protein synthesis through binding to the bacterial 16S rRNA, and by disrupting the integrity of bacterial cell membranes.
    [Show full text]
  • Nationwide Epidemiology of Carbapenem Resistant Klebsiella
    Galani et al. BMC Infectious Diseases (2019) 19:167 https://doi.org/10.1186/s12879-019-3801-1 RESEARCH ARTICLE Open Access Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance Irene Galani1,3*† , Konstantina Nafplioti1†, Panagiota Adamou1, Ilias Karaiskos2, Helen Giamarellou2, Maria Souli1 and Study Collaborators Abstract Background: To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals. Methods: Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR. Results: Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ≤2 mg/L, with MIC50/MIC90 of 0.5/4 mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ≤8 mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC50/MIC90, 4/> 256) and amikacin (S, 18.0%; MIC50/MIC90, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs ≥64 mg/L for plazomicin, and harbored rmtB (n = 22) or armA (n = 1).
    [Show full text]
  • Antibiotics Currently in Clinical Development
    A data table from Feb 2018 Antibiotics Currently in Global Clinical Development Note: This data visualization was updated in December 2017 with new data. As of September 2017, approximately 48 new antibiotics1 with the potential to treat serious bacterial infections are in clinical development. The success rate for clinical drug development is low; historical data show that, generally, only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trials) will be approved for patients.* Below is a snapshot of the current antibiotic pipeline, based on publicly available information and informed by external experts. It will be updated periodically, as products advance or are known to drop out of development. Because this list is updated periodically, endnote numbers may not be sequential. In September 2017, the antibiotics pipeline was expanded to include products in development globally. Please contact [email protected] with additions or updates. Expected activity Expected activity against CDC Development against resistant Drug name Company Drug class Target urgent or WHO Potential indication(s)?5 phase2 Gram-negative critical threat ESKAPE pathogens?3 pathogen?4 Approved for: Acute bacterial skin and skin structure infections; other potential Baxdela Approved June 19, Melinta Bacterial type II Fluoroquinolone Possibly No indications: community-acquired bacterial (delafloxacin) 2017 (U.S. FDA) Therapeutics Inc. topoisomerase pneumonia and complicated urinary tract infections6 Approved for: Complicated urinary Rempex tract infections including pyelonephritis; Vabomere Pharmaceuticals β-lactam (carbapenem) other potential indications: complicated Approved Aug. 30, (Meropenem + Inc. (wholly owned + β-lactamase inhibitor PBP; β-lactamase Yes Yes (CRE) intra-abdominal infections, hospital- 2017 (U.S.
    [Show full text]
  • Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors
    molecules Review Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors Sandra G. Zárate 1, M. Luisa De la Cruz Claure 2, Raúl Benito-Arenas 3, Julia Revuelta 3, Andrés G. Santana 3,* and Agatha Bastida 3,* 1 Facultad de Tecnología-Carrera de Ingeniería Química, Universidad Mayor Real y Pontificia de San Francisco Xavier de Chuquisaca, Regimiento Campos 180, Casilla 60-B, Sucre, Bolivia; [email protected] 2 Facultad de Ciencias Químico Farmacéuticas y Bioquímicas, Universidad Mayor Real y Pontificia de San Francisco Xavier de Chuquisaca, Dalence 51, Casilla 497, Sucre, Bolivia; [email protected] 3 Departmento de Química Bio-Orgánica, Instituto de Química Orgánica General (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; [email protected] (R.B.-A.); [email protected] (J.R.) * Correspondence: [email protected] (A.G.S.); [email protected] (A.B.); Tel: +34-915-612-800 (A.B.) Received: 7 November 2017; Accepted: 26 January 2018; Published: 30 January 2018 Abstract: Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes.
    [Show full text]
  • Pharmacodynamics of Plazomicin and a Comparator Aminoglycoside, Amikacin, Studied in an in Vitro Pharmacokinetic Model of Infection
    International Journal of Antimicrobial Agents 54 (2019) 626–632 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag Pharmacodynamics of plazomicin and a comparator aminoglycoside, amikacin, studied in an in vitro pharmacokinetic model of infection Alan R. Noel a, Marie Attwood a, Karen E. Bowker a, Aryun Kim b, Kevin M. Krause b, ∗ Alasdair P. MacGowan a, a Bristol Centre for Antimicrobial Research & Evaluation (BCARE), Severn Infection Sciences Partnership, Southmead Hospital, Bristol BS10 5NB, UK b Achaogen, 1 Tower Place, Suite 300, South San Francisco, CA 94080, USA a r t i c l e i n f o a b s t r a c t Article history: The new aminoglycoside plazomicin shows in vitro potency against multidrug-resistant Enterobacteri- Received 3 April 2019 ales. The exposure–response relationship of plazomicin and the comparator aminoglycoside amikacin Accepted 3 July 2019 was determined for Escherichia coli , while for Klebsiella pneumoniae only plazomicin was tested. An in vitro pharmacokinetic model was used. Five E. coli strains (two meropenem-resistant) and five K. pneu- Editor: Prof. H. Derendorf moniae strains (two meropenem-resistant) with plazomicin MICs of 0.5–4 mg/L were used. Antibacterial effect was assessed by changes in bacterial load and bacterial population profile. The correlation between Keywords: 2 ≥ Plazomicin change in initial inoculum after 24 h of drug exposure and the AUC/MIC ratio was good (plazomicin R 2 Aminoglycoside 0.8302; amikacin R ≥ 0.9520). Escherichia coli plazomicin AUC/MIC ratios for 24-h static, –1, –2 and –3 Pharmacodynamics log drop were 36.1 ± 18.4, 39.3 ± 20.9, 41.2 ± 21.9 and 44.8 ± 24.3, respectively, and for amikacin were In vitro model 49.5 ± 12.7, 55.7 ± 14.8, 64.1 ± 19.2 and 73.3 ± 25.3.
    [Show full text]
  • Gram Positive Cocci (GPC) Gram Neg (Rods = GNR) Anaerobes
    Gram Positive Cocci (GPC) Gram Neg (rods = GNR) Anaerobes Atypicals Classification Antibiotic Cluster Streptococcus Entero- Resp Enteric Non- Bacteroides, Mycoplasma = Staph β↓ & α-hemolytic↓ coccus (cocci) GI flora enteric Clostridium Legionella Beta-Lactams General Spectrum MSSA Group pneumo, faecalis H. flu, E. coli, Pseud- (non-dfficile) Chlamydia Penicillins of Activity → only A / B Viridans only M. cat Klebsiella omonas Peptostrep. (pneumonia) Natural Penicillin G IV/ PenVK PO +/- ++ + + 0 0 0 + 0 Anti- Oxacillin/Nafcillin IV, ++ ++ + 0 0 0 0 0 0 Staphylococcal Dicloxacillin PO Aminopenicillins Amp/Amoxicillin IV/PO 0 ++ + ++ +R +/- 0 + 0 Anti-Pseudomonal Piperacillin/Ticarcillin IV 0 + + + + + ++R + 0 Beta-Lactamase Clavulanate IV/PO, sulbactam Increase Inc by Increase Increase Inhibitor added tazobactam, vaborbactam IV by + + by + by + Cephalosporins Cefazolin IV/ ++ ++ +/- 0 +/- + 0 0 0 1st Generation Cephalexin PO 2nd Generation Cefuroxime IV/PO + ++ + 0 + + 0 +/- 0 Cephamycins Cefoxitin/Cefotetan IV 0 + 0 0 + + 0 + 0 3rd Generation Ceftriaxone/Cefotaxime IV + ++ ++ 0 ++ ++R 0 +/- 0 (PO in between 2nd Ceftazidime IV (+ Avibactam 0 + 0 0 ++ ++R ++R 0 0 and 3rd gen) for Carb-Resistant Enterics) 4th Generation Cefepime IV + ++ ++ 0 ++ ++ ++R 0 0 Novel Ceftolozane-tazo/Cefiderocol 0 + + 0 ++ ++ ++ +/- 0 Carbapenems Imipenem, Meropenem IV + + + +/- ++ ++ ++R ++ 0 (+rele/vaborbactam for CRE) Ertapenem IV + ++ ++ 0 ++ ++ 0 ++ 0 Monobactam Aztreonam IV 0 0 0 0 ++ ++R + 0 0 Non β-Lactams Includes MRSA Both sp. Aminoglycosides Gentamicin,
    [Show full text]
  • Recent Advances in the Development of Antibacterial Agents
    ISSN: 0975-8585 Research Journal of Pharmaceutical, Biological and Chemical Sciences Recent Advances in the Development of Antibacterial Agents. Avin S, A Avinash, Navin Patil, Sushil Kiran Kunder, Anurag Pathak, and KL Bairy*. Department of Pharmacology, Kasturba Medical College, Manipal, Karnataka, India. ABSTRACT Antibacterials are one of the most commonly prescribed groups of medications, especially in developing nations, owing to the vast number of microbial diseases prevalent in the community. Ever since the discovery of the phenomenal antibacterial, penicillin, there has been a great rise in the number of antibacterials in the market. In this era, where roadblocks like chemo-resistance and mutations plague medicine, scientists across the world are looking to adapt lateral approaches in encountering diseases. This review article brings to limelight, the recent advances in the field of antibacterial drug development, from the year 2007 till date. Keywords: Oritavancin, Tedizolid, Dalbavancin, Raxibacumab, Bedaquiline, Ceftaroline *Corresponding author September - October 2015 RJPBCS 6(5) Page No. 1220 ISSN: 0975-8585 INTRODUCTION Infectious diseases are among the leading causes of mortality worldwide, especially in developing nations where second line antibacterial drugs against resistant bacteria are generally either unavailable or unaffordable. The emergence of multi-drug resistance (MDR) in both community-acquired and hospital- acquired infections has outpaced the development and delivery of new drugs to the clinic. While the market potential for new antibacterial drugs is estimated to be several billions of dollars, the discovery pipelines of most major pharmaceutical companies are running near empty. The paucity of new antibacterial drugs has led the Infectious Disease Society of America (IDSA) and other bodies to call for action in rebuilding the infrastructure and efforts to develop next generation drugs [1].
    [Show full text]