Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections

Journal of Antimicrobial Chemotherapy

Volumn 72, Issue 9, 2017, Pages 2616-2626

  Sims, Matthew ^a   Mariyanovski, Valeri ^b   McLeroth, Patrick ^c   Akers, Wayne ^c   Lee, Yu Chieh ^c   Brown, Michelle L ^d   Du, Jiejun ^d   Pedley, Alison ^d   Kartsonis, Nicholas A ^d   Paschke, Amanda ^d  

^a WILLIAM BEAUMONT HOSPITAL   (United States)

^b UNIVERSITY HOSPITAL ALEXANDROVSKA   (Bulgaria)

^c 206 Carnegie Center   (United States)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ANTIBIOTIC AGENT; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; CILASTATIN PLUS IMIPENEM; CILASTATIN PLUS IMIPENEM PLUS RELEBACTAM; CIPROFLOXACIN; CREATININE; GLUCOSE; PLACEBO; PROTEIN; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; AZABICYCLO DERIVATIVE; BETA LACTAMASE INHIBITOR; CILASTATIN; CILASTATIN, IMIPENEM DRUG COMBINATION; IMIPENEM; MK-7655;

ABDOMINAL PAIN; ACUTE PYELONEPHRITIS; ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ANTIBIOTIC THERAPY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BACTERIURIA; BILIRUBIN BLOOD LEVEL; CHRONOPHARMACOLOGY; CLINICAL OUTCOME; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSGEUSIA; ERADICATION THERAPY; ERYTHROCYTE URINE LEVEL; EXPLORATORY RESEARCH; FEMALE; FEVER; GLUCOSE URINE LEVEL; HEADACHE; HUMAN; HYPERTENSION; INFECTION SENSITIVITY; INFLUENZA; INTENTION TO TREAT ANALYSIS; LEUKOCYTE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; PHASE 2 CLINICAL TRIAL; PROSPECTIVE STUDY; PROTEIN URINE LEVEL; RANDOMIZED CONTROLLED TRIAL; RASH; SENSITIVITY ANALYSIS; SIDE EFFECT; THROMBOCYTOSIS; TREATMENT DURATION; TREATMENT RESPONSE; URINARY TRACT INFECTION; ADOLESCENT; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DRUG COMBINATION; GRAM NEGATIVE INFECTION; INTRAVENOUS DRUG ADMINISTRATION; MICROBIOLOGY; MIDDLE AGED; PYELONEPHRITIS; VERY ELDERLY; YOUNG ADULT;

ADMINISTRATION, INTRAVENOUS; ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTI-BACTERIAL AGENTS; AZABICYCLO COMPOUNDS; BETA-LACTAMASE INHIBITORS; CILASTATIN; DOUBLE-BLIND METHOD; DRUG COMBINATIONS; DRUG THERAPY, COMBINATION; FEMALE; GRAM-NEGATIVE BACTERIAL INFECTIONS; HUMANS; IMIPENEM; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; PYELONEPHRITIS; URINARY TRACT INFECTIONS; YOUNG ADULT;

EID: 85040143612     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkx139     Document Type: Article

References (39)

1. Pendleton JN, Gorman SP, Gilmore BF. Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther 2013; 11: 297-308
2. Rottier WC, Ammerlaan HS, Bonten MJ. Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae and patient outcome: a metaanalysis. JAntimicrobChemother 2012; 67: 1311-20
3. Patel TS, Nagel JL. Clinical outcomes of Enterobacteriaceae infections stratified by carbapenemMICs. JClinMicrobiol 2015; 53: 201-5
4. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilatorassociated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416
5. Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patientswith cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52: e56-93
6. Solomkin JS, Mazuski JE, Bradley JS et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50: 133-64
7. Hsueh P, Hoban D, Carmeli Y et al. Consensus review of the epidemiology and appropriate antimicrobial therapy of complicated urinary tract infections in Asia-Pacific region. J Infect 2011; 63: 114-23
8. Gupta K, Hooton TM, Naber KG et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011; 52: e103-20
9. Jacob JT, Klein E, Laxminarayan R et al. Vital signs: carbapenem-resistant Enterobacteriaceae. MMWRMorb MortalWkly Rep 2013; 62: 165-70
10. CDC. Antibiotic Resistance Threats in the United States. 2013; http://www. cdc. gov/drugresistance/threat-report-2013/
11. Tzouvelekis LS, Markogiannakis A, PsichogiouMet al. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 2012; 25: 682-707
12. Overturf GD. Carbapenemases: a brief review for pediatric infectious disease specialists. Pediatr Infect Dis J 2010; 29: 68-70
13. Bradford PA, Urban C, Mariano N et al. Imipenemresistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC β-lactamase, and the loss of an outer membrane protein. Antimicrob Agents Chemother 1997; 41: 563-9
14. Crowley B, Benedi VJ, Domenech-Sanchez A. Expression of SHV-2 β-lactamase and of reduced amounts of OmpK36 porin in Klebsiella pneumoniae results in increased resistance to cephalosporins and carbapenems. Antimicrob Agents Chemother 2002; 46: 3679-82
15. Zavascki AP, Carvalhaes CG, Picao RC et al. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistancemechanisms and implications for therapy. Expert Rev Anti Infect Ther 2010; 8: 71-93
16. Quale J, Bratu S, Gupta J et al. Interplay of efflux system, ampC, and oprD expression in carbapenemresistance of Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 2006; 50: 1633-41
17. Livermore DM, Warner M, Mushtaq S. Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother 2013; 68: 2286-90
18. Bush K. A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens. Int J Antimicrob Agents 2015; 46: 483-93
19. Hirsch EB, Ledesma KR, Chang KT et al. In vitro activity of MK-7655, a novel β-lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram-negative bacteria. Antimicrob Agents Chemother 2012; 56: 3753
20. BlizzardTA, ChenH, KimSet al. Discovery of MK-7655, α β-lactamase inhibitor for combinationwith Primaxin(R). BioorgMed ChemLett 2014; 24: 780-5
21. Lapuebla A, Abdallah M, Olafisoye O et al. Activity of imipenemwith relebactam against Gram-negative pathogens from New York City. Antimicrob Agents Chemother 2015; 59: 5029-31
22. Lucasti C, Vasile L, Sandesc D et al. Phase 2, dose-ranging study of relebactam with imipenem/cilastatin in subjects with complicated intraabdominal infection. Antimicrob Agents Chemother 2016; 60: 6234-43
23. JeanSS, CoombsG, LingTet al. Epidemiology and antimicrobial susceptibility profiles of pathogens causing urinary tract infections in the Asia-Pacific region: Results from the Study forMonitoring Antimicrobial Resistance Trends (SMART), 2010-2013. Int J Antimicrob Agents 2016; 47: 328-34
24. Lob SH, Nicolle LE, Hoban DJ et al. Susceptibility patterns and ESBL rates of Escherichia coli from urinary tract infections in Canada and the United States, SMART 2010-2014. DiagnMicrobiol Infect Dis 2016; 85: 459-65
25. Zowawi HM, Harris PN, RobertsMJ et al. The emerging threat of multidrugresistant Gram-negative bacteria in urology. Nat Rev Urol 2015; 12: 570-84
26. Tandogdu Z, Cek M, Wagenlehner F et al. Resistance patterns of nosocomial urinary tract infections in urology departments: 8-year results of the global prevalence of infections in urology study. World J Urol 2014; 32: 791-801
27. Raman G, Avendano E, Berger S. Appropriate initial antibiotic therapy in hospitalized patients with gram-negative infections: systematic review and meta-analysis. BMC Infect Dis 2015; 15: 395
28. ZilberbergMD, Shorr AF, Micek ST. Multi-drug resistance, inappropriate initial antibiotic therapy andmortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 2014; 18: 596
29. Grabe M, Bishop M, Bjerklund-Johansen T et al. Guidelines for Urological Infections. https://uroweb. org/wp-content/uploads/19-Urological-infections_ LR2. pdf
30. Merck & Co I. PRIMAXINVR I. V. (Imipenem and Cilastatin for Injection). Whitehouse Station, NJ, 2014
31. FDA. 1998. Complicated urinary tract infections and pyelonephritisdeveloping antimicrobial drugs for treatment. In: US Department of Health and Human Services, Food and Drug Administration and Center for Drug Evaluation and Research (CDER) Guidance for Industry. Rockville, MD: Drug Information Branch. Division ofCommunicationsManagement, 1998
32. EMA. Guideline on the Evaluation of Medicinal Products Indicated for Treatment of Bacterial Infections. 2011. http://www. ema. europa. eu/docs/en_ GB/document_library/Scientific_guideline/2009/09/WC500003417. pdf
33. Cox CE, Holloway WJ, Geckler RW. A multicenter comparative study of meropenemand imipenem/cilastatin in the treatment of complicated urinary tract infections in hospitalized patients. Clin Infect Dis 1995; 21: 86-92
34. Cox CE, Corrado ML. Safety and efficacy of imipenem/cilastatin in treatment of complicated urinary tract infections. AmJMed 1985; 78: 92-4
35. Matsumoto T, Muratani T. Newer carbapenems for urinary tract infections. Int J Antimicrob Agents 2004; 24 Suppl 1: S35-8
36. Rogers JD, Meisinger MA, Ferber F et al. Pharmacokinetics of imipenem and cilastatin in volunteers. Rev Infect Dis 1985; 7 Suppl 3: S435-46
37. Norrby SR, Rogers JD, Ferber F et al. Disposition of radiolabeled imipenem and cilastatin in normal human volunteers. Antimicrob Agents Chemother 1984; 26: 707-14
38. Nicolle LE, Bradley S, Colgan R et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005; 40: 643-54
39. Wagenlehner FM, Sobel JD, Newell P et al. Ceftazidime-avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis: RECAPTURE, a Phase 3 randomized trial program. Clin Infect Dis 2016; 63: 754-62