Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria
- 4.8k Downloads
- 58 Citations
Abstract
The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections.
Keywords
Antibiotic Bacteria Resistance MRSA StewardshipAbbreviations
- AST
Antimicrobial susceptibility testing
- BLBLI
β-Lactam/β-lactamase inhibitors
- CDI
Clostridium difficile infection
- CRE
Carbapenem-resistant Enterobacteriaceae
- ECDC
European Center for Diseases Control
- ESBL
Extended-spectrum β-lactamases
- ESBL-PE
Extended-spectrum β-lactamase-producing Εnterobacteriaceae
- EUCAST
European Committee on Antimicrobial Susceptibility Testing
- FDA
Food and Drug Administration
- HAP
Hospital-acquired pneumonia
- HCW
Healthcare workers
- ICU
Intensive care unit
- IDSA
Infectious Diseases Society of America
- KPC
Klebsiella pneumoniae carbapenemase
- MDR
Multidrug-resistant organisms
- MIC
Minimum inhibitory concentration
- MITT
Modified intention to treat
- MRSA
Methicillin-resistant Staphylococcus aureus
- PK/PD
Pharmacokinetic/pharmacodynamic
- SDD
Selective digestive decontamination
- VAP
Ventilator-associated pneumonia
- VIM
Verona integron-mediated metallo-β-lactamase
- VRE
Vancomycin-resistant enterococci
Notes
Acknowledgments
Research made in collaboration with the Critically Ill Patients Study Group (ESGCIP) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
Conflicts of interest
MB serves on scientific advisory boards for AstraZeneca, Bayer, Cubist, Pfizer Inc, MSD, Tetraphase, and Astellas Pharma Inc.; has received funding for travel or speaker honoraria from Algorithm, Angelini, Astellas Pharma Inc., AstraZeneca, Cubist, Pfizer MSD, Gilead Sciences, Novartis, Ranbaxy, and Teva. GP has received funding for travel or speaker honoraria from Astellas, Gilead, MSD, Novartis, and Pfizer. JGM has received speaker honoraria from Astellas, Gilead, MSD, Novartis, and Pfizer and a scientific grant from Astellas. DPN: Consultant, member of the speakers bureau, or has received research grant funding from AstraZeneca, Bayer, Cubist, Actavis, GSK, Medicines Co., Merck, Pfizer, and Tetraphase. JDW has served on advisory boards for Bayer, Cubist, MSD, and Sumitomo Pharma. PE has received funding for advisory board or speaker honoraria from Astellas, MSD, and Pfizer. MHW has received consulting fees from Abbott Laboratories, Actelion, Astellas, Astra-Zeneca, Bayer, Cerexa, Cubist, Durata, The European Tissue Symposium, The Medicines Company, MedImmune, Merck, Motif Biosciences, Nabriva, Optimer, Paratek, Pfizer, Roche, Sanofi-Pasteur, Seres, Summit, and Synthetic Biologics; and lecture fees from Abbott, Alere, Astellas, Astra-Zeneca, and Pfizer; grant support from Abbott, Actelion, Astellas, bioMerieux, Cubist, Da Volterra, The European Tissue Symposium, Merck, and Summit. The other authors declare no conflict of interests.
Supplementary material
References
- 1.Nathan C, Cars O (2014) Antibiotic resistance—problems, progress, and prospects. N Engl J Med 371:1761–1763PubMedGoogle Scholar
- 2.Barber M, Rozwadowska-Dowzenki M (1948) Infection by penicillin-resistant staphylococci. Lancet 2:641–644PubMedGoogle Scholar
- 3.Bassetti M, Nicolau DP, Calandra T (2014) What’s new in antimicrobial use and resistance in critically ill patients? Intensive Care Med 40:422–426PubMedGoogle Scholar
- 4.WHO (2014) Antimicrobial resistance: global report on surveillance. http://www.who.int/drugresistance/documents/surveillancereport/en/
- 5.ECDC (2013) The ECDC EARS-Net report 2013. http://www.ecdc.europa.eu/en/publications/Publications/antimicrobial-resistance-surveillance-europe-2013.pdf
- 6.Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281PubMedGoogle Scholar
- 7.Razazi K, Derde LP, Verachten M, Legrand P, Lesprit P, Brun-Buisson C (2012) Clinical impact and risk factors for colonization with extended-spectrum β-lactamase-producing bacteria in the intensive care unit. Intensive Care Med 38(11):1769–1778PubMedGoogle Scholar
- 8.Woodford N (2008) Successful, multiresistant bacterial clones. J Antimicrob Chemother 61:233–234PubMedGoogle Scholar
- 9.Sundqvist M, Geli P, Andersson DI, Sjölund-Karlsson M, Runehagen A, Cars H, Abelson-Storby K, Cars O, Kahlmeter G (2010) Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use. J Antimicrob Chemother 65(2):350–360PubMedGoogle Scholar
- 10.ESCMID Conference on Reviving Old Antibiotics (2014) 22–24 October 2014, Vienna, Austria. https://www.escmid.org/research_projects/escmid_conferences/reviving_old_antibiotics/scientific_programme/. Accessed 11 Mar 2015
- 11.Buchan BW, Ledeboer NA (2014) Emerging technologies for the clinical microbiology laboratory. Clin Microbiol Rev 27(4):783–822PubMedGoogle Scholar
- 12.La Scola B, Raoult D (2009) Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption time-of-flight mass spectrometry. PLoS One 4:e8041PubMedCentralPubMedGoogle Scholar
- 13.The European Committee on Antimicrobial Susceptibility Testing (EUCAST). http://www.eucast.org. Accessed 11 Mar 2015
- 14.The Clinical Laboratory Standards Institute. http://www.clsi.org. Accessed 11 Mar 2015
- 15.Clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing. http://www.eucast.org/clinical_breakpoints/. Accessed 11 Mar 2015
- 16.Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, Huskins WC, Paterson DL, Fishman NO, Carpenter CF, Brennan PJ, Billeter M, Hooton TM, Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (2007) Guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 44:159–177PubMedGoogle Scholar
- 17.Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med 39:165–228PubMedGoogle Scholar
- 18.Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, Osborn T, Lemeshow S, Chiche JD, Artigas A, Dellinger RP (2014) Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med 40:1623–1633PubMedGoogle Scholar
- 19.Timsit JF, Harbarth S, Carlet J (2014) De-escalation as a potential way of reducing antibiotic use and antimicrobial resistance in ICU. Intensive Care Med 40:1580–1582PubMedGoogle Scholar
- 20.Luyt CE, Bréchot N, Trouillet JL, Chastre J (2014) Antibiotic stewardship in the intensive care unit. Crit Care 18:480PubMedCentralPubMedGoogle Scholar
- 21.Kaki R, Elligsen M, Walker S, Simor A, Palmay L, Daneman N (2011) Impact of antimicrobial stewardship in critical care: a systematic review. J Antimicrob Chemother 66:1223–1230PubMedGoogle Scholar
- 22.Chalfine A, Kitzis MD, Bezie Y, Benali A, Perniceni L, Nguyen JC, Dumay MF, Gonot J, Rejasse G, Goldstein F, Carlet J, Misset B (2012) Ten-year decrease of acquired methicillin-resistant Staphylococcus aureus (MRSA) bacteremia at a single institution: the result of a multifaceted program combining cross-transmission prevention and antimicrobial stewardship. Antimicrob Resist Infect Control 1:18PubMedCentralPubMedGoogle Scholar
- 23.Garnacho-Montero J, Gutierrez- Pizarraya A, Escoresca-Ortega A et al (2013) De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 39:2237Google Scholar
- 24.Kumar A, Roberts D, Wood KE et al (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589–1596PubMedGoogle Scholar
- 25.Tabah A, Koulenti D, Laupland K et al (2012) Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 38:1930–1945PubMedGoogle Scholar
- 26.Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, Perez XL, Sirvent JM (2009) Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med 180:861–866PubMedGoogle Scholar
- 27.Kumar A, Ellis P, Arabi Y, Roberts D et al (2009) Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 136:1237–1248PubMedGoogle Scholar
- 28.Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH (2014) Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 18(6):596PubMedCentralPubMedGoogle Scholar
- 29.Aliberti S, Cilloniz C, Chalmers JD et al (2013) Multidrug-resistant pathogens in hospitalised patients coming from the community with pneumonia: a European perspective. Thorax 68:997–999PubMedGoogle Scholar
- 30.Kollef MH, Sherman G, Ward S et al (1999) Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115:462–474PubMedGoogle Scholar
- 31.Gonçalves-Pereira J, Pereira JM, Ribeiro O, Baptista JP, Froes F, Paiva JA (2014) Impact of infection on admission and of process of care on mortality of patients admitted to the intensive care unit: the INFAUCI study. Clin Microbiol Infect. doi: 10.1111/1469-0691.12738 PubMedGoogle Scholar
- 32.Prkno A, Wacker C, Brunkhorst FM, Schlattmann P (2013) Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock—a systematic review and meta-analysis. Crit Care 17(6):R291PubMedCentralPubMedGoogle Scholar
- 33.Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L (2004) Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 328(7441):668PubMedCentralPubMedGoogle Scholar
- 34.Heyland DK, Dodek P, Muscedere J, Day A, Cook D, Canadian Critical Care Trials Group (2008) Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 36(3):737–744PubMedGoogle Scholar
- 35.Brunkhorst FM, Oppert M, Marx G, Bloos F, Ludewig K, Putensen C, Nierhaus A, Jaschinski U, Meier-Hellmann A, Weyland A, Gründling M, Moerer O, Riessen R, Seibel A, Ragaller M, Büchler MW, John S, Bach F, Spies C, Reill L, Fritz H, Kiehntopf M, Kuhnt E, Bogatsch H, Engel C, Loeffler M, Kollef MH, Reinhart K, Welte T, German Study Group Competence Network Sepsis (SepNet) (2012) Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA 307(22):2390–2399PubMedGoogle Scholar
- 36.Micek ST, Welch EC, Khan J, Pervez M, Doherty JA, Reichley RM, Kollef MH (2010) Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis. Antimicrob Agents Chemother 54(5):1742–1748PubMedCentralPubMedGoogle Scholar
- 37.Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G, Keenan S, Wood G, Arabi Y, Feinstein D, Kumar A, Dodek P, Kravetsky L, Doucette S, Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group (2010) Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med 38(9):1773–1785PubMedGoogle Scholar
- 38.Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M (2012) Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis 55(7):943–950PubMedGoogle Scholar
- 39.Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y (2012) Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 56(4):2108–2113PubMedCentralPubMedGoogle Scholar
- 40.Samonis G, Maraki S, Karageorgopoulos DE, Vouloumanou EK, Falagas ME (2012) Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur J Clin Microbiol Infect Dis 31:695–701PubMedGoogle Scholar
- 41.Durante-Mangoni E, Grammatikos A, Utili R, Falagas ME (2009) Do we still need the aminoglycosides? Int J Antimicrob Agents 33:201–205PubMedGoogle Scholar
- 42.De Waele JJ, Ravyts M, Depuydt P, Blot SI, Decruyenaere J, Vogelaers D (2010) De-escalation after empirical meropenem treatment in the intensive care unit: fiction or reality? J Crit Care 25:641–646PubMedGoogle Scholar
- 43.Gonzalez L, Cravoisy A, Barraud D, Conrad M, Nace L, Lemarie J, Bollaert PE, Gibot S (2013) Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients. Crit Care 17:R140PubMedCentralPubMedGoogle Scholar
- 44.Mokart D, Slehofer G, Lambert J, Sannini A, Chow-Chine L, Brun JP, Berger P, Duran S, Faucher M, Blache JL, Saillard C, Vey N, Leone M (2014) De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive Care Med 40:41–49PubMedGoogle Scholar
- 45.De Waele JJ, Bassetti M, Martin-Loeches I (2014) Impact of de-escalation on ICU patients’ prognosis. Intensive Care Med 40:1583–1585Google Scholar
- 46.Leone M, Bechis C, Baumstarck K, Lefrant JY, Albanese J, Jaber S, Lepape A, Constantin JM, Papazian L, Bruder N, Allaouchiche B, Bezulier K, Antonini F, Textoris J, Martin C (2014) De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 40:1399–1408PubMedGoogle Scholar
- 47.Kollef MH (2014) What can be expected from antimicrobial de-escalation in the critically ill? Intensive Care Med 40:92–95PubMedGoogle Scholar
- 48.Thabit AK, Crandon JL, Nicolau DP (2015) Antimicrobial resistance: impact on clinical and economic outcomes and the need for new antimicrobials. Exp Opin Pharmacother 16:159–177Google Scholar
- 49.Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, Hope WW, Farkas A, Neely MN, Schentag JJ, Drusano G, Frey OR, Theuretzbacher U, Kuti JL, International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases (2014) Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 14:498–509PubMedGoogle Scholar
- 50.Udy AA, Baptista JP, Lim NL, Joynt GM, Jarrett P, Wockner L, Boots RJ, Lipman J (2014) Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations. Crit Care Med 42:520–527PubMedGoogle Scholar
- 51.Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J, DALI Study (2014) DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 58:1072–1083PubMedGoogle Scholar
- 52.Nicasio AM, Eagye KJ, Nicolau DP, Shore E, Palter M, Pepe J, Kuti JL (2010) A pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients infected with ventilator-associated pneumonia. J Crit Care 25:69–77PubMedGoogle Scholar
- 53.MacVane SH, Kuti JL, Nicolau DP (2014) Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation. Int J Antimicrob Agents 43(2):105–113PubMedGoogle Scholar
- 54.Eggimann P, Pittet D (2001) Infection control in the ICU. Chest 120:2059–2093PubMedGoogle Scholar
- 55.Siegel JD, Rhinehart E, Jackson M, Chiarello L, Health Care Infection Control Practices Advisory Committee (2007) 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control 35:S65–S164PubMedGoogle Scholar
- 56.Price JR, Golubchik T, Cole K, Wilson DJ, Crook DW, Thwaites GE, Bowden R, Walker AS, Peto TE, Paul J, Llewelyn MJ (2014) Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit. Clin Infect Dis 58(5):609–618PubMedCentralPubMedGoogle Scholar
- 57.Longtin Y, Sax H, Allegranzi B, Schneider F, Pittet D, Videos in clinical medicine (2011) Hand hygiene. N Engl J Med 364:e24PubMedGoogle Scholar
- 58.Derde LP, Cooper BS, Goossens H, Malhotra-Kumar S, Willems RJ, Gniadkowski M, Hryniewicz W, Empel J, Dautzenberg MJ, Annane D, Aragão I, Chalfine A, Dumpis U, Esteves F, Giamarellou H, Muzlovic I, Nardi G, Petrikkos GL, Tomic V, Martí AT, Stammet P, Brun-Buisson C, Bonten MJ, MOSAR WP3 Study Team (2014) Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 14:31–39PubMedCentralPubMedGoogle Scholar
- 59.Daneman N, Sarwar S, Fowler RA, Cuthbertson BH, SuDDICU Canadian Study Group (2013) Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis 13(4):328–341PubMedGoogle Scholar
- 60.Bassetti M, Righi E (2014) SDD and colistin resistance: end of a dream? Intensive Care Med 40(7):1066–1067PubMedGoogle Scholar
- 61.Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, Bartlett JG, Edwards J Jr, Infectious Diseases Society of America (2008) The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 46:155–164PubMedGoogle Scholar
- 62.Piddock LJ (2012) The crisis of no new antibiotics—what is the way forward? Lancet Infect Dis 12:249–253PubMedGoogle Scholar
- 63.Infectious Diseases Society of America (2010) The 10 × ´20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis 50:1081–1083Google Scholar
- 64.The Pew Charitable Trusts (2014) Tracking the pipeline of antibiotics in development. http://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2014/03/12/tracking-the-pipeline-of-antibiotics-in-development. Accessed September 2014
- 65.Poulakou G, Bassetti M, Righi E, Dimopoulos G (2014) Current and future treatment options for infections caused by multidrug-resistant Gram-negative pathogens. Future Microb 9:1053–1069Google Scholar
- 66.Luyt CE, Clavel M, Guntupalli K (2009) Pharmacokinetics and lung delivery of PDDS-aerosolize amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia. Crit Care 13(6):R200 (iol 9:1053–1069)Google Scholar
- 67.Zahar JR, Lortholary O, Martin C, Potel G, Plesiat P, Nordmann P (2009) Addressing the challenge of extended-spectrum beta-lactamases. Curr Opin Investig Drugs 10:172–180PubMedGoogle Scholar
- 68.Rodríguez-Baño J, Picón E, Navarro MD, López-Cerero L, Pascual A, ESBL-REIPI Group (2012) Impact of changes in CLSI and EUCAST breakpoints for susceptibility in bloodstream infections due to extended-spectrum β-lactamase-producing Escherichia coli. Clin Microbiol Infect 18:894–900PubMedGoogle Scholar
- 69.Shiber S, Yahav D, Avni T, Leibovici L, Paul M (2015) β-Lactam/β-lactamase inhibitors versus carbapenems for the treatment of sepsis: systematic review and meta-analysis. J Antimicrob Chemother 70:41–47PubMedGoogle Scholar
- 70.Rodríguez-Baño J, Picón E, Gijón P, Hernández JR, Ruíz M, Peña C, Almela M, Almirante B, Grill F, Colomina J, Giménez M, Oliver A, Horcajada JP, Navarro G, Coloma A, Pascual A, Spanish Network for Research in Infectious Diseases (REIPI) (2010) Community-onset bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: risk factors and prognosis. Clin Infect Dis 50:40–48PubMedGoogle Scholar
- 71.Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME (2012) Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review meta-analysis of randomized controlled trials. J Antimicrob Chemother 67:2793–2803PubMedGoogle Scholar
- 72.Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC (2013) Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 56:488–495PubMedGoogle Scholar
- 73.Goethaert K, Van Looveren M, Lammens C, Jansens H, Baraniak A, Gniadkowski M, Van Herck K, Jorens PG, Demey HE, Ieven M, Bossaert L, Goossens H (2006) High-dose cefepime as an alternative treatment for infections caused by TEM-24 ESBL-producing Enterobacter aerogenes in severely-ill patients. Clin Microbiol Infect 12:56–62PubMedGoogle Scholar
- 74.Chopra T, Marchaim D, Veltman J, Johnson P, Zhao JJ, Tansek R, Hatahet D, Chaudhry K, Pogue JM, Rahbar H, Chen TY, Truong T, Rodriguez V, Ellsworth J, Bernabela L, Bhargava A, Yousuf A, Alangaden G, Kaye KS (2012) Impact of cefepime therapy on mortality among patients with bloodstream infections caused by extended-spectrum-β-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother 56:3936–3942PubMedCentralPubMedGoogle Scholar
- 75.Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, Cornaglia G, Garau J, Gniadkowski M, Hayden MK, Kumarasamy K, Livermore DM, Maya JJ, Nordmann P, Patel JB, Paterson DL, Pitout J, Villegas MV, Wang H, Woodford N, Quinn JP (2013) Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 13:785–796PubMedGoogle Scholar
- 76.Tumbarello M, Trecarichi EM, Tumietto F, Del Bono V, De Rosa FG, Bassetti M, Losito AR, Tedeschi S, Saffioti C, Corcione S, Giannella M, Raffaelli F, Pagani N, Bartoletti M, Spanu T, Marchese A, Cauda R, Viscoli C, Viale P (2014) Predictive models for identification of hospitalized patients harboring KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 58:3514–3520PubMedCentralPubMedGoogle Scholar
- 77.Tzouvelekis LS, Markogiannakis A, Piperaki E, Souli M, Daikos GL (2014) Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect 20:862–872PubMedGoogle Scholar
- 78.Daikos GL, Tsaousi S, Tzouvelekis LS, Anyfantis I, Psichogiou M, Argyropoulou A, Stefanou I, Sypsa V, Miriagou V, Nepka M, Georgiadou S, Markogiannakis A, Goukos D, Skoutelis A (2014) Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother 58:2322–2328PubMedCentralPubMedGoogle Scholar
- 79.Dubrovskaya Y, Chen TY, Scipione MR, Esaian D, Phillips MS, Papadopoulos J, Mehta SA (2013) Risk factors for treatment failure of polymyxin B monotherapy for carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother 57:5394–5397PubMedCentralPubMedGoogle Scholar
- 80.Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M, Oikonomou A, Poulakou G, Roilides E, Giamarellou H (2014) Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. Int J Antimicrob Agents 43:52–59PubMedGoogle Scholar
- 81.Plachouras D, Karvanen M, Friberg LE, Papadomichelakis E, Antoniadou A, Tsangaris I, Karaiskos I, Poulakou G, Kontopidou F, Armaganidis A, Cars O, Giamarellou H (2009) Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother 53:3430–3436PubMedCentralPubMedGoogle Scholar
- 82.Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, Nation RL (2011) Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 55:3284–3294PubMedCentralPubMedGoogle Scholar
- 83.Dalfino L, Puntillo F, Mosca A, Monno R, Spada ML, Coppolecchia S, Miragliotta G, Bruno F, Brienza N (2012) High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis 54:1720–1726Google Scholar
- 84.Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC (2013) Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem–cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother 57:1756–1762PubMedCentralPubMedGoogle Scholar
- 85.Giamarellou H, Galani L, Baziaka F, Karaiskos I (2013) Effectiveness of a double-carbapenem regimen for infections in humans due to carbapenemase-producing pandrug-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother 57:2388–2390PubMedCentralPubMedGoogle Scholar
- 86.Giannella M, Trecarichi EM, De Rosa FG, Del Bono V, Bassetti M, Lewis RE, Losito AR, Corcione S, Saffioti C, Bartoletti M, Maiuro G, Cardellino CS, Tedeschi S, Cauda R, Viscoli C, Viale P, Tumbarello M (2014) Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study. Clin Microbiol Infect 20:1357–1362PubMedGoogle Scholar
- 87.Tumbarello M, De Pascale G, Trecarichi EM, Spanu T, Antonicelli F, Maviglia R, Pennisi MA, Bello G, Antonelli M (2013) Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med 39:682–692PubMedGoogle Scholar
- 88.Eagye KJ, Banevicius MA, Nicolau DP (2012) Pseudomonas aeruginosa is not just in the intensive care unit any more: implications for empirical therapy. Crit Care Med 40:1329–1332PubMedGoogle Scholar
- 89.Bliziotis IA, Petrosillo N, Michalopoulos A, Samonis G, Falagas ME (2011) Impact of definite therapy with beta-lactam monotherapy or combination with an aminoglycoside or a quinolone for Pseudomonas aeruginosa Bacteremia. PLOS One 6:e2640Google Scholar
- 90.Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagacé-Wiens PR, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch JP 3rd, Karlowsky JA (2014) Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs 74:31–51PubMedGoogle Scholar
- 91.Karagoz G, Kadanali A, Dede B, Sahin OT, Comoglu S, Altug SB, Naderi S (2014) Extensively drug-resistant Pseudomonas aeruginosa ventriculitis and meningitis treated with intrathecal colistin. Int J Antimicrob Agents 43(1):93–94PubMedGoogle Scholar
- 92.Garnacho-Montero J, Ortiz-Leyba C, Fernández-Hinojosa E, Aldabó-Pallás T, Cayuela A, Marquez-Vácaro JA, Garcia-Curiel A, Jiménez-Jiménez FJ (2005) Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings. Intensive Care Med 31:649–655PubMedGoogle Scholar
- 93.Martin-Loeches I, Deja M, Koulenti D, Dimopoulos G, Marsh B, Torres A, Niederman, Rello J, EU-VAP Study Investigators (2013) Potentially resistant microorganisms in intubated patients with hospital-acquired pneumonia: the interaction of ecology, shock and risk factors. Intensive Care Med 39(4):672–681PubMedGoogle Scholar
- 94.Dijkshoorn L, Nemec A, Seifert H (2007) An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 5:939–951PubMedGoogle Scholar
- 95.Gales AC, Jones RN, Sader HS (2011) Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance Program (2006–09). J Antimicrob Chemother 66:2070–2074PubMedGoogle Scholar
- 96.Jones RN, Flonta M, Gurler N, Cepparulo M, Mendes RE, Castanheira M (2014) Resistance surveillance program report for selected European nations. Diagn Microbiol Infect Dis 78:429–436PubMedGoogle Scholar
- 97.Sandri AM, Landersdorfer CB, Jacob J, Boniatti MM, Dalarosa MG, Falci DR, Behle TF, Bordinhão RC, Wang J, Forrest A, Nation RL, Li J, Zavascki AP (2013) Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis 57:524–531PubMedGoogle Scholar
- 98.Cai Y, Wang R, Liang B, Bai N, Liu Y (2011) Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease. Antimicrob Agents Chemother 55:1162–1172PubMedCentralPubMedGoogle Scholar
- 99.Prasad P, Sun J, Danner RL, Natanson C (2012) Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 54:1699–1709PubMedCentralPubMedGoogle Scholar
- 100.Medicines and Healthcare Products Regulatory Agency (2011) Tigecycline: increased mortality in clinical trials—use only when other antibiotics are unsuitable. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON111761. Accessed 23 Dec 2014
- 101.De Pascale G, Montini L, Pennisi M, Bernini V, Maviglia R, Bello G, Spanu T, Tumbarello M, Antonelli M (2014) High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care 18:R90PubMedCentralPubMedGoogle Scholar
- 102.Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, Bassetti M, Malacarne P, Petrosillo N, Galdieri N, Mocavero P, Corcione A, Viscoli C, Zarrilli R, Gallo C, Utili R (2013) Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis 57:349–358PubMedGoogle Scholar
- 103.López-Cortés LE, Cisneros JM, Fernández-Cuenca F, Bou G, Tomás M, Garnacho-Montero J, Pascual A, Martínez-Martínez L, Vila J, Pachón J, Rodríguez Baño J, On behalf of the GEIH/REIPI-Ab2010 Group (2014) Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort. J Antimicrob Chemother 69:3119–3126PubMedGoogle Scholar
- 104.Petrosillo N, Giannella M, Antonelli M, Antonini M, Barsic B, Belancic L, Inkaya AC, De Pascale G, Grilli E, Tumbarello M, Akova M (2014) Clinical experience of colistin-glycopeptide combination in critically ill patients infected with Gram-negative bacteria. Antimicrob Agents Chemother 58:851–858PubMedCentralPubMedGoogle Scholar
- 105.National Institute for Health and Care Excellence (2014) Hospital-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus: telavancin. http://www.nice.org.uk/advice/esnm44. Accessed 23 December 2014
- 106.Bally M, Dendukuri N, Sinclair A, Ahern SP, Poisson M, Brophy J (2012) A network meta-analysis of antibiotics for treatment of hospitalised patients with suspected or proven meticillin-resistant Staphylococcus aureus infection. Int J Antimicrob Agents 40:479–495PubMedGoogle Scholar
- 107.Gurusamy KS, Koti R, Toon CD, Wilson P, Davidson BR (2013) Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds. Cochrane Database Syst Rev 8:CD009726Google Scholar
- 108.Gurusamy KS, Koti R, Toon CD, Wilson P, Davidson BR (2013) Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds. Cochrane Database Syst Rev 11:CD010427Google Scholar
- 109.Logman JF, Stephens J, Heeg B, Haider S, Cappelleri J, Nathwani D, Tice A, van Hout BA (2010) Comparative effectiveness of antibiotics for the treatment of MRSA complicated skin and soft tissue infections. Curr Med Res Opin 26:1565–1578PubMedGoogle Scholar
- 110.Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, McGee WT, Reisman A, Chastre J (2012) Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 54(5):621–629PubMedGoogle Scholar
- 111.Kalil AC, Van Schooneveld TC, Fey PD, Rupp ME (2014) Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis. JAMA 312:1552–1564PubMedGoogle Scholar
- 112.Sánchez García M, De la Torre MA, Morales G, Peláez B, Tolón MJ, Domingo S, Candel FJ, Andrade R, Arribi A, García N, Martínez Sagasti F, Fereres J, Picazo J (2010) Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA 303(22):2260–2264PubMedGoogle Scholar
- 113.van Hal SJ, Paterson DL, Lodise TP (2013) Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother 57:734–744PubMedCentralPubMedGoogle Scholar
- 114.Public Health England (2013) Updated guidance on the management and treatment of C. difficile infection. https://www.gov.uk/government/publications/clostridium-difficile-infection-guidance-on-management-and-treatment. Accessed 23 December 2014
- 115.Wilcox MH (2014) The trials and tribulations of treating Clostridium difficile infection-one step backward, one step forward, but still progress. Clin Infect Dis 59:355–357PubMedGoogle Scholar
- 116.Britt NS, Steed ME, Potter EM, Clough LA (2014) Tigecycline for the treatment of severe and severe complicated Clostridium difficile infection. Infect Dis Ther 3:321–331Google Scholar
- 117.Herpers BL, Vlaminckx B, Burkhardt O et al (2009) Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. Clin Infect Dis 48(12):1732–1735PubMedGoogle Scholar
- 118.Apisarnthanarak A, Razavi B, Mundy LM (2002) Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature. Clin Infect Dis 35:690–996PubMedGoogle Scholar
- 119.Lamontagne F, Labbe AC, Haeck O, Lesur O, Lalancette M, Patino C, Leblanc M, Laverdière M, Pépin J (2007) Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 245:267–272PubMedCentralPubMedGoogle Scholar
- 120.Bhangu A, Nepogodiev D, Gupta A, Torrance A, Singh P (2012) West Midlands Research Collaborative Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium difficile colitis. Br J Surg 99:1501–1513PubMedGoogle Scholar
- 121.Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS (2011) Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg 254:423–427PubMedGoogle Scholar