DOCSLIB.ORG

Doripenem a Review of Its Use in the Treatment of Bacterial Infections

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Doripenem a Review of Its Use in the Treatment of Bacterial Infections Drugs 2008; 68 (14): 2021-2057 ADIS DRUG EVALUATION 0012-6667/08/0014-2021/$53.45/0 © 2008 Adis Data Information BV. All rights reserved. Doripenem A Review of its Use in the Treatment of Bacterial Infections Susan J. Keam Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USA Various sections of the manuscript reviewed by: Y. Ike, Gunma University Graduate School of Medicine, Maebashi, Japan; T. Matsumoto, Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan; G. Poulakou, 4th Department of Internal Medicine, Athens Medical School, Attikon University General Hospital, Athens, Greece; J.S. Solomkin, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; F. Van Bambeke, Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de Louvain, Brussels, Belgium; G.G. Zhanel, Medical Microbiology Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada. Data Selection Sources: Medical literature published in any language since 1980 on ‘doripenem’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Wolters Kluwer Health | Adis). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Search strategy: MEDLINE, EMBASE and AdisBase search term was ‘doripenem’. Searches were last updated 4 August 2008. Selection: Studies in patients with bacterial infections who received doripenem. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included. Index terms: Doripenem, complicated intra-abdominal infections, complicated skin and skin structure infections, complicated urinary tract infections, nosocomial pneumonia, ventilator-associated pneumonia, gynaecological and obstetric infections, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability. Contents Summary ..................................................................................2022 1. Introduction ............................................................................2025 2. Pharmacodynamic Profile ...............................................................2025 2.1 Mechanism of Action ...............................................................2025 2.2 In Vitro Antibacterial Activity .........................................................2025 2.2.1 Gram-Negative Bacteria ......................................................2027 2.2.2 Gram-Positive Bacteria ........................................................2029 2.2.3 Anaerobic Bacteria ...........................................................2029 2.2.4 Synergistic Activity ............................................................2031 2.2.5 Bactericidal Activity and Post-Antibiotic Effect ...................................2031 2.3 Resistance Issues ....................................................................2033 2.4 In Vivo Antibacterial Activity .........................................................2035 2.5 Other Effects .......................................................................2035 3. Pharmacokinetic Properties ..............................................................2035 3.1 Distribution .........................................................................2035 3.2 Metabolism and Elimination ..........................................................2036 3.3 Special Patient Populations ..........................................................2036 3.3.1 In Renal Impairment ...........................................................2036 3.4 Potential Drug Interactions ...........................................................2037 2022 Keam 4. Pharmacodynamic/Pharmacokinetic Relationship .........................................2037 5. Therapeutic Efficacy ....................................................................2038 5.1 Serious Lower Respiratory Tract Infections .............................................2039 5.1.1 Nosocomial Pneumonia .......................................................2041 5.2 Complicated Intra-Abdominal Infection ..............................................2043 5.3 Complicated Urinary Tract Infection ..................................................2044 5.4 Other Infections ....................................................................2046 5.4.1 Skin and Skin Structure Infections ...............................................2046 5.4.2 Obstetric and Gynaecological Infection ........................................2046 5.4.3 Sepsis and Endocarditis ........................................................2046 5.4.4 Ear, Nose and Throat Infections .................................................2047 5.4.5 Dental and Oral Surgical Infection ..............................................2047 5.4.6 Ophthalmic Infection ..........................................................2047 6. Tolerability ..............................................................................2047 7. Dosage and Administration ..............................................................2048 8. Place of Doripenem in the Management of Bacterial Infections .............................2049 Summary Abstract Doripenem, a parenteral, broad-spectrum antibacterial agent of the carbapenem family, is indicated as empirical therapy in serious bacterial infections in adults. Doripenem is indicated in Japan for use as a single agent in intra-abdominal infections (IAIs), lower respiratory tract infections (including nosocomial pneu- monia), complicated urinary tract infections (cUTIs) and a variety of other bacterial infections, such as complicated skin and skin structure infections (cSSSIs), obstetric and gynaecological infections, serious ear, nose and throat infections, sepsis and endocarditis, dental and oral surgical infection, and ophthalmic infection caused by various susceptible strains of Gram-negative, Gram-positive or anaerobic bacteria. Doripenem is indicated in the US for the treatment of complicated IAIs (cIAIs) or cUTIs, including pyelonephritis, caused by susceptible strains of designated pathogens, and in the EU for the treatment of nosocomial pneumonia (including ventilator-associated pneumonia [VAP]), cIAIs or cUTIs. Doripenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, including extended-spectrum β-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, and anaerobic pathogens. The drug also has a low propensity to select for resistance and is suitable for the prolonged infusions that may be required to achieve pharmacodynamic/pharmacokinetic targets for bactericidal activity (and therefore efficacy) against pathogens with increased MICs (minimum concentrations required to inhibit the pathogens). Doripenem is no less effective than other antibacterial agents, including meropenem, imipenem/ cilastin, piperacillin/tazobactam or levofloxacin in a wide range of serious bacter- ial infections, such as complicated lower respiratory infections, nosocomial pneumonia (including VAP), cIAIs and cUTIs, and is well tolerated. Thus, doripenem is a valuable addition to the options available for the empirical treatment of serious bacterial infections in hospitalized patients. © 2008 Adis Data Information BV. All rights reserved. Drugs 2008; 68 (14) Doripenem: A Review 2023 Pharmacological Doripenem demonstrated good in vitro activity against clinically relevant Enter- Properties obacteriaceae (Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp. and Serratia spp.). The minimum concentration inhibiting 90% of strains (MIC90) was generally ≤0.5 mg/L and susceptibility rates were 93–100%. Doripenem was active against ESBL- and AmpC-producing Enterobacteriaceae, with little or no change in MIC90 values compared with non-ESBL- and non-AmpC-producing strains. Doripenem was also active against Haemophilus influenzae, Moraxella catarrhalis and Pro- videncia spp. (MIC90 ≤1.56 mg/L). Activity against non-fermentative Gram- negative pathogens was more limited. Doripenem MIC90 values were 0.2–12.5 mg/L against susceptible isolates of Pseudomonas aeruginosa and 8–64 mg/L against carbapenem- or ceftazidime-resistant isolates. Doripenem activity against Acinetobacter spp. was more limited in Europe and the Americas (MIC90 1–32 mg/L) than in Japan (MIC90 ≤3.13 mg/L). Doripenem demonstrated good in vitro activity against Gram-positive patho- gens, including Staphylococcus aureus (methicillin/oxacillin-susceptible iso- lates), Streptococcus pneumoniae (including penicillin-, ceftriaxone- or multidrug-resistant strains), S. pyogenes and S. agalactiae (MIC90 ≤1 mg/L; susceptibility rate of 100%), but had limited activity against Enterococcus faecalis (MIC90 4–16 mg/L). Activity against S. epidermidis varied according to geo- graphic region (e.g. for methicillin or oxacillin-susceptible isolates, MIC90 values were 0.03 mg/L in Europe and the Americas and ≤0.031–12.5 mg/L in Japan). Doripenem lacked activity against methicillin or oxacillin-resistant staphylococci and E. faecium. Doripenem demonstrated in vitro activity against a range of anaerobic patho- gens, including B. fragilis, B. thetaiotaomicron and
Load more

Recommended publications
  • Polymyxin B in Combination with Doripenem Against Heteroresistant Acinetobacter Baumannii: Pharmacodynamics of New Dosing Strategies
    J Antimicrob Chemother 2016; 71: 3148–3156 doi:10.1093/jac/dkw293 Advance Access publication 3 August 2016 Polymyxin B in combination with doripenem against heteroresistant Acinetobacter baumannii: pharmacodynamics of new dosing strategies Gauri G. Rao1,2, Neang S. Ly1,2,Ju¨rgen B. Bulitta1,3, Rachel L. Soon1,2, Marie D. San Roman1,2, Patricia N. Holden1,2, Cornelia B. Landersdorfer4, Roger L. Nation4, Jian Li4, Alan Forrest1,5 and Brian T. Tsuji1,2* 1Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA; 2The New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA; 3Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA; 4Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia; 5Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, NC, USA *Corresponding author. Tel: +1-716-881-7543; Fax: +1-716-849-6890; E-mail: [email protected] Received 13 October 2015; returned 3 January 2016; revised 14 June 2016; accepted 19 June 2016 Objectives: Polymyxin B is being increasingly utilized as a last resort against resistant Gram-negative bacteria. We examined the pharmacodynamics of novel dosing strategies for polymyxin B combinations to maximize efficacy and minimize the emergence of resistance and drug exposure against Acinetobacter baumannii. Methods: The pharmacodynamics of polymyxin B together with doripenem were evaluated in time–kill experi- ments over 48 h against 108 cfu/mL of two polymyxin-heteroresistant A.
    [Show full text]
  • Occurrence of PER-1 Producing Clinical Isolates of Pseudomonas Aeruginosa in Japan and Their Susceptibility to Doripenem
    J. Antibiot. 59(12): 791–796, 2006 THE JOURNAL OF ORIGINAL ARTICLE ANTIBIOTICS Occurrence of PER-1 Producing Clinical Isolates of Pseudomonas aeruginosa in Japan and their Susceptibility to Doripenem Yoshinori Yamano, Toru Nishikawa, Takaji Fujimura, Takashi Yutsudou, Masakatsu Tsuji, Hideaki Miwa Received: July 13, 2006 / Accepted: November 20, 2006 © Japan Antibiotics Research Association Abstract The acquisition of resistance by extended- Keywords Pseudomonas aeruginosa, doripenem, ESBL, spectrum b-lactamases (ESBL) has been reported primarily PER-1, in vivo activity for Enterobacteriaceae, but there are few reports on the isolation of ESBL-producing Pseudomonas aeruginosa. PER-1-type ESBL producing P. aeruginosa has been found Introduction in various regions around the world but there are no reports of clinical isolates in Japan. During our susceptibility Pseudomonas aeruginosa is an opportunistic pathogen surveillance studies over a 10 year period, we found causing serious infection in immunocompromised hosts. P. four clinical isolates resistant to ceftazidime due to aeruginosa has intrinsic resistance to many antibiotics and production of PER-1. They were resistant to ceftazidime produces a variety of virulence factors. The intrinsic but susceptible in the presence of clavulanic acid, a class resistance of P. aeruginosa to various antibiotics is A b-lactamase inhibitor. The strains had the ability to generally due to its low outer membrane permeability and hydrolyze ceftazidime. They also had the gene for PER-1- the production of efflux pumps [1]. Although there are type ESBL. This is the first report of the isolation of various antipseudomonal agents such as b-lactams, PER-1 producing strains in Japan. These four strains were quinolones, and aminoglycosides, resistance to these resistant to ceftazidime, cefepime and aztreonam with antibiotics is acquired by P.
    [Show full text]
  • In-Vitro Activity of Doripenem Vs. Imipenem & Meropenem Against
    International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571 Original Research Article In-Vitro Activity of Doripenem vs. Imipenem & Meropenem against Clinical Isolates of Pseudomonas and Other Oxidase-Positive Gram- Negative Bacilli Priya Singh1, Richa Misra2 1Department of Microbiology, Swargiya Dadasaheb Kalmegh Smruti Dental College & Hospital, Nagpur, India 2Department of Microbiology, Division Bacteriology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, India Corresponding Author: Richa Misra ABSTRACT Background & objectives: Doripenem is approved by United States Food and Drug Administration(US FDA) for the treatment of complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI) and in Europe for ventilator-associated pneumonia (VAP).We attempted to compare the in vitro activity of doripenem with imipenem and meropenem using current CLSI guidelines among clinical isolates of Pseudomonas spp. and other oxidase positive Gram-negative bacilli from clinical samples. Methods: Eighty consecutive clinical isolates were included in the study. Samples included were pus (n=29), blood (n=7), urine (n=24) and 20 sputum (n=20). MIC values of the imipenem, meropenem and doripenem were determined by E tests. Out of 72 Polymyxin B sensitive isolates 34 were Pseudomonas aeruginosa, 30 Fluorescent group and 8 Alcaligenes group. Polymyxin B (n=8) resistant isolates were identified as Burkholderia group. Pseudomonas aeruginosa ATCC 29853 was used as quality control strain. Results: In the Polymyxin B sensitive group (n=72), 29.1%, 23.6% and 26.3% isolates were susceptible to imipenem, meropenem and doripenem respectively. In the Polymyxin B resistant group (n=8) only one isolate was sensitive to imipenem and meropenem while 5 were moderately sensitive to doripenem.
    [Show full text]
  • Ceftaroline Fosamil for the Treatment of Gram-Positive Endocarditis: CAPTURE Study Experience
    International Journal of Antimicrobial Agents 53 (2019) 644–649 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag Ceftaroline fosamil for the treatment of Gram-positive endocarditis: CAPTURE study experience ∗ Christopher J. Destache a, David J. Guervil b, Keith S. Kaye c, a School of Pharmacy and Health Professions, Creighton University, Omaha, NE, USA b Memorial Hermann-Texas Medical Center, Houston, TX, USA c Wayne State University and Detroit Medical Center, Detroit, MI, USA a r t i c l e i n f o a b s t r a c t Article history: Background: The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective Received 3 October 2018 endocarditis is reported from CAPTURE, a retrospective study conducted in the USA. Accepted 27 January 2019 Methods: Data, including patient demographics, medical history, risk factors, microbiological aetiology and clinical outcomes, were collected by review of patient charts between September 2013 and February Editor: Professor Matthew Falagas 2015. Results: Patients ( n = 55) with Gram-positive endocarditis were treated with CPT-F. The most common Keywords: risk factors were intravascular devices (43.6%), diabetes mellitus (40.0%) and injection drug use (38.2%). Ceftaroline fosamil Gram-positive endocarditis The most commonly isolated pathogens were meticillin-resistant Staphylococcus aureus (MRSA; 80%), Meticillin-resistant Staphylococcus aureus meticillin-susceptible S. aureus (MSSA; 7.3%) and coagulase-negative staphylococci (7.3%). CPT-F was given Meticillin-susceptible Staphylococcus aureus as first-line therapy in 7.3% of patients and as second-line or later therapy in 92.7% of patients, and as CAPTURE study monotherapy in 41.8% of patients and as concurrent therapy in 58.2% of patients.
    [Show full text]
  • Carbapenem-Resistant Enterobacteriaceae Investigative Guidelines December 2019
    PUBLIC HEALTH DIVISION Acute and Communicable Disease Prevention Carbapenem-Resistant Enterobacteriaceae Investigative Guidelines December 2019 1. DISEASE REPORTING 1.1 Purpose of Reporting and Surveillance 1. To prevent transmission of infections with carbapenem-resistant Enterobacteriaceae (CRE) between patients, within or among health care facilities, or between health care facilities and the community. 2. To prevent CRE from becoming endemic in Oregon, necessitating empiric use of even broader- spectrum antibiotics. 3. To identify outbreaks and potential sources or sites of ongoing transmission. 4. To better characterize the epidemiology of these infections. 1.2 Laboratory and Physician Reporting Requirements 1. Providers and laboratories must report cases to local public health authorities (LPHAs) within one working day. 2. Clinical and reference laboratories must forward isolates from any sterile or non-sterile site (e.g., urine, blood, sputum, endotracheal aspirate, BAL, wound) that meet the confirmed CRE case definition below along with the automated test system susceptibility printouts (Vitek or Microscan report) to the Oregon State Public Health Laboratory (OSPHL). 3. Isolates of Proteus, Providencia, or Morganella which show only imipenem non-susceptibility, in the absence of resistance to another carbapenem, do not need to be submitted. 1.3 Local Public Health Authority Reporting and Follow-Up Responsibilities 1. LPHAs will confirm that a case meets the case definition by reviewing the isolate's susceptibility information (antibiogram) as necessary, or in consultation with the ACDP epidemiologist. Both minimum inhibitory concentration (MIC) values and interpretations are needed to verify a case meets the definition. (See Confirmed Case §3.1.) 2. If a case meets the case definition, the LPHA will investigate.
    [Show full text]
  • Doribax (Doripenem)
    ———————WARNINGS AND PRECAUTIONS——————— HIGHLIGHTS OF PRESCRIBING INFORMATION • Serious hypersensitivity (anaphylactic) reactions have been reported These highlights do not include all the information needed to use ® with carbapenems and other beta-lactams (5.1) DORIBAX safely and effectively. See full prescribing information for ® • Seizures have been reported with carbapenems, including doripenem DORIBAX . (5.2) ® DORIBAX® (doripenem for injection) Powder, For Solution for • It has been shown that co-administration of DORIBAX with valproic Intravenous use acid reduces the serum concentration of valproic acid. Patients with Initial U.S. Approval: 2007 seizure disorders controlled with valproic acid or sodium valproate will therefore be at an increased risk for breakthrough seizures. (5.3) —————————————— • Clostridium difficile-associated diarrhea (ranging from mild diarrhea to To reduce the development of drug-resistant bacteria and maintain the fatal colitis): Evaluate if diarrhea occurs (5.4) effectiveness of DORIBAX® and other antibacterial drugs, DORIBAX® should be used only to treat or prevent infections that are proven or strongly ——————————ADVERSE REACTIONS————————— suspected to be caused by bacteria. Most common adverse reactions (≥ 5%) are headache, nausea, diarrhea, rash and phlebitis. —————————RECENT MAJOR CHANGES———————— • Warnings and Precautions To report SUSPECTED ADVERSE REACTIONS, contact Janssen • Seizures (5.2) 04/2013 Pharmaceutical, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. —————————INDICATIONS
    [Show full text]
  • Antimicrobial Activity of Doripenem Against Bacterial Isolates from Humans and Animals
    The Journal of Antibiotics (2010) 63, 631–632 & 2010 Japan Antibiotics Research Association All rights reserved 0021-8820/10 $32.00 www.nature.com/ja COMMUNICATION TO THE EDITOR Antimicrobial activity of doripenem against bacterial isolates from humans and animals The Journal of Antibiotics (2010) 63, 631–632; doi:10.1038/ja.2010.97; published online 18 August 2010 b-Lactam antibiotics, such as penicillins, pathogens including Enterobacteriaceae,non- A total of 938 isolates were tested, includ- cephalosporins and carbapenems, are the fermenting gram-negative, anaerobes, and ing 522 enterococci and 416 E. coli (62 of largest family of antimicrobial agents, and many gram-positive both in vivo and which produced extended-spectrum b-lacta- have been widely used in this clinical prac- in vitro, including some carbapenem resis- mases (ESBLs)) were previously recovered tice.1 However, the emergence and the tant.2–5 Recently, doripenem was indicated in from fecal samples of human and animal increased frequency of antimicrobial resis- the United States and Europe for the treat- origin and characterized by using specific tance has become a serious health problem. ment of intraabdominal and complicated primers to species identification and detec- For this reason, the development of new urinary tract infections including pyelone- tion of antibiotic resistant genes.6 Doripenem antimicrobial drugs becomes a worldwide phritis, and approved in the Europe for standard powder was provided by Johnson priority. Doripenem (formerly known as patients with nosocomial pneumonia includ- & Johnson Pharmaceutical Research & Deve- S-4661) is a new synthetic 1-b-methyl carba- ing ventilator-associated pneumonia.4 lopment, LLC (Raritan, NJ, USA).
    [Show full text]
  • AR Phenotype Definitions
    Antibiotic Resistance & Patient Safety Portal Antibiotic Resistance HAI Data The following are definitions for the phenotypes listed in the Antibiotic Resistance & Patient Safety Portal. For all pathogens included in the AR HAI dataset, there is a select group of antimicrobials for which susceptibility test results must be reported to the National Healthcare Safety Network (NHSN); these pathogen-antimicrobial combinations are then used to define the selected phenotypes. Susceptibility results for each pathogen were reported to NHSN using the final category interpretations (see key below). For more information about the AR Patient Safety Portal Antibiotic Resistance HAI dataset, visit: http://www.cdc.gov/hai/surveillance. Phenotype Analytical Definitions Key (S) Susceptible (I) Intermediate (R) Resistant (NS) Non-Susceptible Escherichia coli Carbapenem-resistant (CRE) Any isolate that tested (R) to at least 1 of these: imipenem, meropenem, doripenem, ertapenem Cephalosporin-resistant Any isolate that tested (I) or (R) to at least 1 of these: ceftriaxone, ceftazidime, cefepime, cefotaxime Fluoroquinolone-resistant Any isolate that tested (I) or (R) to at least 1 of these: ciprofloxacin, levofloxacin, moxifloxacin Multidrug-resistant (MDR) Any isolate that tested either (I)* or (R) to at least 1 drug in at least 3 of these categories: 1. Extended-spectrum cephalosporins (ceftriaxone, ceftazidime, cefepime, cefotaxime) 2. Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) 3. Aminoglycosides (amikacin, gentamicin, tobramycin) 4. *Carbapenems (isolate must have tested (R) to imipenem, meropenem, doripenem, or ertapenem) 5. Piperacillin/tazobactam 1 August 2021 Enterobacter Carbapenem-resistant (CRE) Any isolate that tested (R) to at least 1 of these: imipenem, meropenem, doripenem, ertapenem Cefepime-resistant Any isolate that tested (I) or (R) to cefepime Multidrug-resistant (MDR) Any isolate that tested either (I)* or (R) to at least 1 drug in at least 3 of these categories: 1.
    [Show full text]
  • Effective Reporting of Antimicrobial Susceptibility Test Results
    Laboratory Detection and Reporting of Carbapenem-Resistant Enterobacteriaceae (CRE) CLSI Outreach Working Group Spring, 2016 1 After review of this program, you will be able to: List current CLSI recommendations for antimicrobial susceptibility testing (AST) and reporting of CRE. Describe the differences between CRE (Carbapenem-resistant Enterobacteriaceae) and CPE (Carbapenemase-producing Enterobacteriaceae). Explain the significance of CRE and CPE from clinical and epidemiological perspectives. Describe when and where to go for help when physicians need more information than your laboratory can provide for a potential CRE isolate. 2 Acronyms Used in this Presentation CRE = Carbapenem-R Enterobacteriaceae CPE = Carbapenemase-Producing Enterobacteriaceae Also CRO, CRKP, CPKP, CPO – “O” = organism – “KP”= Klebsiella pneumoniae 3 β-Lactams and GNRs Basic Concepts 4 Common β-Lactam Agents Active Against Gram-Negative Rods (GNR) β-lactam Penicillins Inhibitor Combos Cephalosporins Cephamycin Carbapenems Amoxicillin Amoxicillin-clav Cefazolin (1) Cefoxitin Doripenem Ampicillin Ampicillin- sulb Cefuroxime (2) Cefotetan Ertapenem Piperacillin Piperacillin-tazo Cefotaxime (3) Monobactam Imipenem Ticarcillin Ticarcillin-clav Ceftazidime (3) Aztreonam Meropenem Ceftolozane-tazo Ceftriaxone (3) Ceftaz-avibactam Cefepime (4) 5 β-Lactams β-Lactam β-Lactam (Penicillin) (Penicillin) All β-lactams contain a 4-membered β-lactam ring that is essential for activity 6 Different β-Lactams Penicillins Cephalosporins Cephamycins Carbapenems Monobactam 7 Gram-Negative Bacterial Cell Outer membrane Chromosomal DNA Plasmid DNA Periplasmic space Ribosomes Cell wall 50S 50S 50S (peptidoglycan) 30S 30S 30S Cell membrane Cartoon courtesy of L. Westblade 8 β-Lactam Activity Against Gram-Negatives β-lactam Porin Channel or Efflux Pump Outer membrane Periplasmic space Penicillin-Binding Proteins (PBPs) Cell wall Cartoon courtesy of L.
    [Show full text]
  • Comparative In-Vitro Activity of Imipenem and Doripenem Against Esbl Producing Klebsiella Isolates from a Tertiary Hospital in Ilorin, Nigeria A
    August 2015 EAST AFRICAN MEDICAL JOURNAL 415 East African Medical Journal Vol. 92 No. 8 August 2015 COMPARATIVE IN-VITRO ACTIVITY OF IMIPENEM AND DORIPENEM AGAINST ESBL PRODUCING KLEBSIELLA ISOLATES FROM A TERTIARY HOSPITAL IN ILORIN, NIGERIA A. Fadeyi, C. P. Zumuk, R. A. Raheem, C. Nwabuisi, Department of Medical Microbiology and Parasitology and O. O. Desalu, Department of Medicine, University of Ilorin, Ilorin, Nigeria COMPARATIVE IN-VITRO ACTIVITY OF IMIPENEM AND DORIPENEM AGAINST ESBL PRODUCING KLEBSIELLA ISOLATES FROM A TERTIARY HOSPITAL IN ILORIN, NIGERIA A. FADEYI, C. P. ZUMUK, R. A. RAHEEM, C. NWABUISI and O. O. DESALU ABSTRACT Background: Doripenem is a recent carbapenem not commercially available in Nigeria with broad spectrum antibacterial activity against various clinical infections. Carbapenems have been shown to be the last line of agents against ESBL producing organisms. Objective: To determine the in-vitro activity of Imipenem and Doripenem against ESBL producing Klebsiella spp. Design: A cross-sectional laboratory based study. Setting: The University of Ilorin Teaching Hospital, a major tertiary hospital in Ilorin, the capital of Kwara state in Nigeria. Subjects: All strains of Klebsiella spp isolated from all clinical specimens collected at the hospital laboratory non– repetitively. Result: Doripenem had a superior in-vitro activity compared to imipenem with MIC 50/90 value of 0.0125/0.023 while imipenem was found to be 0.19/0.38 which was statistically different. Conclusion: The result obtained in this study is similar to those from other studies and therefore re-affirms the superior activity of doripenem compared to imipenem and should therefore be introduced as a better alternative to imipenem against ESBL producing organisms.
    [Show full text]
  • Carbapenem-Resistant Enterobacteriaceae (Cre)
    OREGON PUBLIC HEALTH DIVISION REPORTING FOR Local health department information CARBAPENEM-RESISTANT For a list of local health department phone numbers go to www.healthoregon.org/diseasereporting. ENTEROBACTERIACEAE (CRE) Background CRE case definition for Oregon laboratories as of 7/1/2015 Bacteria of the Enterobacteriaceae family (see list below) that are: nfection with carbapenem-resistant (CRE) is a growing Enterobacteriaceae 1 health care challenge. To date in the United • Resistant to any carbapenem including doripenem, ertapenem, imipenem or I using the current M100-S252 CLSI breakpoints3; OR States, CRE have mainly caused health care- meropenem associated infections, usually affecting those • Positive for a carbapenemase4 gene sequence by a nucleic acid amplification test; OR with compromised immune systems, chronic • Positive for carbapenemase production by Carba NP on any Enterobacteriaceae or by medical conditions, frequent or prolonged stays Modified Hodge if the isolate is an Eschericha coli or Klebsiella spp. in health care settings, invasive medical devices (e.g., ventilators or intravenous catheters), or a Current breakpoints (µg/mL) (M100-S25)2 history of taking antibiotics for long periods. CRE Carbapenems Susceptible Intermediate Resistant can cause a wide variety of infections, including Doripenem ≤1 2 ≥4 pneumonia, bacteremia, urinary tract and Ertapenem ≤0.5 1 ≥2 surgical-site infections. CRE are resistant to most, Imipenem ≤1 2 ≥4 and in some cases, all available antibiotics. Meropenem ≤1 2 ≥4 In the health care setting, patients may carry Current disk diffusion zone diameters (mm) (M100-S25)2 CRE on the skin or in body secretions such as Carbapenems Susceptible Intermediate Resistant sputum, urine or stool.
    [Show full text]
  • Imipenem Kills Pseudomonas€Aeruginosa
    P0262 Imipenem kills Pseudomonas aeruginosa (PA) substantially faster than meropenem and doripenem most likely due to more rapid outer-membrane (OM) penetration Yuli Qian1, Bartolome Moya1, Lijie Zhang1, Xun Tao1, Tae Hwan Kim1, Yuanyuan Jiao1, Dhruvitkumar Sutaria1, Jürgen Bulitta*1 1University of Florida, Pharmaceutics, Orlando, United States Background: Rapid initial bacterial killing may be life-saving in severe infections which are commonly caused by PA in immune-compromised patients. Carbapenems can kill PA rapidly at low and high (>107 CFU/mL) bacterial densities and very few studies showed that carbapenems penetrated the OM of PA more rapidly than other beta-lactams. We aimed to compare the rate of initial killing of PA by imipenem, meropenem and doripenem and estimate the rate of OM penetration via mechanism-based PK/PD models (MBM). These three carbapenems are known to have very similar IC50s for PBPs 1a, 1b, 2, 3 and 4 in PA. Materials/methods: In vitro static concentration time-kill studies over 8 h used a growth control and six carbapenem concentrations between 1 and 24 mg/L all in duplicate against wild-type PAO1 PA (inoculum: 107.2 CFU/mL). Viable counts, carbapenem concentrations (via LC-MS/MS) and AmpC beta-lactamase activity were determined over time for each carbapenem. MBM were developed in the S-ADAPT software. Results: Imipenem at 2, 4 and 8 mg/L killed PA substantially faster during the first 5 hours than doripenem and meropenem (Figure). At 16 mg/L, all three carbapenems achieved near identical maximum rates of killing. Imipenem up-regulated AmpC beta-lactamase more extensively than doripenem and meropenem; this caused considerable degradation of imipenem at 1, 2 and 4 mg/L starting at 2 to 4 h; degradation was minimal for meropenem and doripenem.
    [Show full text]