Optimizing antimicrobial therapy of sepsis and septic shock: Focus on antibiotic combination therapy

Seminars in Respiratory and Critical Care Medicine

Volumn 36, Issue 1, 2015, Pages 154-166

  Vazquez Grande, Gloria ^a   Kumar, Anand ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

antibiotic; combination therapy; life threatening infection; septic shock; survival

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC AGENT; BETA LACTAM ANTIBIOTIC; CEPHALOSPORIN DERIVATIVE; MEROPENEM; PIPERACILLIN PLUS TAZOBACTAM; VANCOMYCIN;

ANTIBIOTIC THERAPY; ANTIMICROBIAL THERAPY; ARTICLE; CLINICAL TRIAL (TOPIC); DISEASE MODEL; DRUG POTENCY; ENDOCARDITIS; GRAM NEGATIVE SEPSIS; HUMAN; IN VITRO STUDY; INFECTION; META ANALYSIS (TOPIC); MORBIDITY; MORTALITY; PATHOGEN CLEARANCE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; SEPSIS; SEPTIC SHOCK; SHOCK; THERAPY DELAY;

EID: 84964282461     PISSN: 10693424     EISSN: 10989048     Source Type: Journal    
DOI: 10.1055/s-0034-1398742     Document Type: Article

References (142)

1. Sands K. E.; Bates D. W.; Lanken P. N.; et al. Academic Medical Center Consortium Sepsis Project Working Group. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA: 1997; 278 3 234 240
2. Brun-Buisson C.; Doyon F.; Carlet J.; et al. French ICU Group for Severe Sepsis. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. JAMA: 1995; 274 12 968 974
3. Annane D.; Aegerter P.; Jars-Guincestre M. C.; Guidet B.; CUB-Réa Network. Current epidemiology of septic shock: the CUB-Réa Network. Am J Respir Crit Care Med: 2003; 168 2 165 172
4. Finland M.; Jones W. F. Jr, Barnes M. W. Occurrence of serious bacterial infections since introduction of antibacterial agents. J Am Med Assoc: 1959; 170 18 2188 2197
5. Hemminki E.; Paakkulainen A. The effect of antibiotics on mortality from infectious diseases in Sweden and Finland. Am J Public Health: 1976; 66 12 1180 1184
6. Kreger B. E.; Craven D. E.; McCabe W. R. Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. Am J Med: 1980; 68 3 344 355
7. Martin G. S.; Mannino D. M.; Eaton S.; Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med: 2003; 348 16 1546 1554
8. Angus D. C.; Linde-Zwirble W. T.; Lidicker J.; Clermont G.; Carcillo J.; Pinsky M. R. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med: 2001; 29 7 1303 1310
9. Eichacker P. Q.; Natanson C. Increasing evidence that the risks of rhAPC may outweigh its benefits. Intensive Care Med: 2007; 33 3 396 399
10. Gårdlund B. Activated protein C (Xigris) treatment in sepsis: a drug in trouble. Acta Anaesthesiol Scand: 2006; 50 8 907 910 A
11. Kumar A. An alternate pathophysiologic paradigm of sepsis and septic shock: implications for optimizing antimicrobial therapy. Virulence: 2014; 5 1 80 97
12. Bone R. C.; Sibbald W. J.; Sprung C. L. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest: 1992; 101 6 1481 1483
13. Levy M. M.; Fink M. P.; Marshall J. C.; et al. SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med: 2003; 31 4 1250 1256
14. van der Poll T.; van Deventer S. JH. Cytokines and anticytokines in the pathogenesis of sepsis. Infect Dis Clin North Am: 1999; 13 2 413 426, ix
15. van der Poll T. Coagulation and inflammation. J Endotoxin Res: 2001; 7 4 301 304
16. Hotchkiss R. S.; Karl I. E. The pathophysiology and treatment of sepsis. N Engl J Med: 2003; 348 2 138 150
17. Remick D. G. Pathophysiology of sepsis. Am J Pathol: 2007; 170 5 1435 1444
18. Freeman B. D.; Natanson C. Anti-inflammatory therapies in sepsis and septic shock. Expert Opin Investig Drugs: 2000; 9 7 1651 1663
19. Khatib R.; Johnson L. B.; Fakih M. G.; et al. Persistence in Staphylococcus aureus bacteremia: incidence, characteristics of patients and outcome. Scand J Infect Dis: 2006; 38 1 7 14
20. Chowers M. Y.; Gottesman B.; Paul M.; Weinberger M.; Pitlik S.; Leibovici L. Persistent bacteremia in the absence of defined intravascular foci: clinical significance and risk factors. Eur J Clin Microbiol Infect Dis: 2003; 22 10 592 596
21. Kullberg B. J.; Sobel J. D.; Ruhnke M.; et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet: 2005; 366 9495 1435 1442
22. Reboli A. C.; Rotstein C.; Pappas P. G.; et al. Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med: 2007; 356 24 2472 2482
23. Levine D. P.; Fromm B. S.; Reddy B. R. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med: 1991; 115 9 674 680
24. Wiggers C. J. Experimental haemorrhage shock. In: Physiology of shock: The Commonwealth Fund. New York, NY Harvard University Press: 1950; 121 143
25. De Luca G.; Suryapranata H.; Ottervanger J. P.; Antman E. M. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation: 2004; 109 10 1223 1225
26. Simoons M. L.; Serruys P. W.; vd Brand M.; et al. Improved survival after early thrombolysis in acute myocardial infarction. A randomised trial by the Interuniversity Cardiology Institute in The Netherlands. Lancet: 1985; 2 8455 578 582
27. Sampalis J. S.; Lavoie A.; Williams J. I.; Mulder D. S.; Kalina M. Impact of on-site care, prehospital time, and level of in-hospital care on survival in severely injured patients. J Trauma: 1993; 34 2 252 261
28. Vallés J.; Rello J.; Ochagavía A.; Garnacho J.; Alcalá M. A. Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival. Chest: 2003; 123 5 1615 1624
29. Ulloa L.; Tracey K. J. The cytokine profile: a code for sepsis. Trends Mol Med: 2005; 11 2 56 63
30. Wang H.; Czura C. J.; Tracey K. J. Lipid unites disparate syndromes of sepsis. Nat Med: 2004; 10 2 124 125
31. Simon P. M.; Delude R. L.; Lee M.; et al. GenIMS Investigators. Duration and magnitude of hypotension and monocyte deactivation in patients with community-acquired pneumonia. Shock: 2011; 36 6 553 559
32. Kumar A.; Haery C.; Paladugu B.; et al. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis: 2006; 193 2 251 258 A
33. Ovstebo R.; Brandtzaeg P.; Brusletto B.; et al. Use of robotized DNA isolation and real-time PCR to quantify and identify close correlation between levels of Neisseria meningitidis DNA and lipopolysaccharides in plasma and cerebrospinal fluid from patients with systemic meningococcal disease. J Clin Microbiol: 2004; 42 7 2980 2987
34. Lala H. M.; Mills G. D.; Barratt K.; Bonning J.; Manikkam N. E.; Martin D. Meningococcal disease deaths and the frequency of antibiotic administration delays. J Infect: 2007; 54 6 551 557
35. Rello J.; Lisboa T.; Lujan M.; et al. DNA-Neumococo Study Group. Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest: 2009; 136 3 832 840
36. DuPont H. L.; Spink W. W. Infections due to gram-negative organisms: an analysis of 860 patients with bacteremia at the University of Minnesota Medical Center, 1958-1966. Medicine (Baltimore): 1969; 48 4 307 332 A
37. Marra A. R.; Edmond M. B.; Forbes B. A.; Wenzel R. P.; Bearman G. ML. Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection. J Clin Microbiol: 2006; 44 4 1342 1346
38. Khatib R.; Riederer K.; Saeed S.; et al. Time to positivity in Staphylococcus aureus bacteremia: possible correlation with the source and outcome of infection. Clin Infect Dis: 2005; 41 5 594 598
39. Liao C-H, Lai C-C, Hsu M-S.; et al. Correlation between time to positivity of blood cultures with clinical presentation and outcomes in patients with Klebsiella pneumoniae bacteraemia: prospective cohort study. Clin Microbiol Infect: 2009; 15 12 1119 1125
40. Peralta G.; Roiz M. P.; Sánchez M. B.; et al. Time-to-positivity in patients with Escherichia coli bacteraemia. Clin Microbiol Infect: 2007; 13 11 1077 1082
41. Martínez J. A.; Soto S.; Fabrega A.; et al. Relationship of phylogenetic background, biofilm production, and time to detection of growth in blood culture vials with clinical variables and prognosis associated with Escherichia coli bacteremia. J Clin Microbiol: 2006; 44 4 1468 1474
42. Chuang Y-C, Chang S-C, Wang W-K. Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia. Crit Care Med: 2012; 40 8 2273 2280
43. Ehrlich P. Address in pathology on chemiotherapy.: delivered before the Seventeenth International Congress of Medicine. BMJ: 1913; 2 2746 353 359
44. Ammerlaan H.; Seifert H.; Harbarth S.; et al. European Practices of Infections with Staphylococcus aureus (SEPIA) Study Group. Adequacy of antimicrobial treatment and outcome of Staphylococcus aureus bacteremia in 9 Western European countries. Clin Infect Dis: 2009; 49 7 997 1005 A
45. Elhanan G.; Sarhat M.; Raz R. Empiric antibiotic treatment and the misuse of culture results and antibiotic sensitivities in patients with community-acquired bacteraemia due to urinary tract infection. J Infect: 1997; 35 3 283 288
46. Blot S.; Vandewoude K.; De Bacquer D.; Colardyn F. Nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in critically ill patients: clinical outcome and length of hospitalization. Clin Infect Dis: 2002; 34 12 1600 1606
47. Blot S.; Depuydt P.; Vogelaers D.; et al. Colonization status and appropriate antibiotic therapy for nosocomial bacteremia caused by antibiotic-resistant gram-negative bacteria in an intensive care unit. Infect Control Hosp Epidemiol: 2005; 26 6 575 579
48. Haddy R. I.; Nadkarni D. D.; Mann B. L.; et al. Clostridial bacteremia in the community hospital. Scand J Infect Dis: 2000; 32 1 27 30
49. Kumar A.; Ellis P.; Arabi Y.; et al. Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest: 2009; 136 5 1237 1248
50. Romero-Vivas J.; Rubio M.; Fernandez C.; Picazo J. J. Mortality associated with nosocomial bacteremia due to methicillin-resistant Staphylococcus aureus. Clin Infect Dis: 1995; 21 6 1417 1423
51. Nguyen M. H.; Peacock J. E. Jr, Tanner D. C.; et al. Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study. Arch Intern Med: 1995; 155 22 2429 2435
52. Garnacho-Montero J.; García-Cabrera E.; Diaz-Martín A.; et al. Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: importance of early adequate treatment. Scand J Infect Dis: 2010; 42 3 185 192
53. Kumar A.; Zarychanski R.; Light B.; et al. Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med: 2010; 38 9 1773 1785
54. Kollef M. H. Broad-spectrum antimicrobials and the treatment of serious bacterial infections: getting it right up front. Clin Infect Dis: 2008; 47 1 01 S3 S13
55. Paul M.; Shani V.; Muchtar E.; Kariv G.; Robenshtok E.; Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother: 2010; 54 11 4851 4863
56. Kollef M. H.; Sherman G.; Ward S.; Fraser V. J. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest: 1999; 115 2 462 474
57. Kollef M. H.; Morrow L. E.; Niederman M. S.; et al. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest: 2006; 129 5 1210 1218
58. Singh N.; Rogers P.; Atwood C. W.; Wagener M. M.; Yu V. L. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med: 2000; 162 2, Pt 1 505 511
59. Aarts M-A, Brun-Buisson C.; Cook D. J.; et al. Antibiotic management of suspected nosocomial ICU-acquired infection: does prolonged empiric therapy improve outcome? Intensive Care Med: 2007; 33 8 1369 1378
60. Joung M. K.; Lee J. A.; Moon S-Y.; et al. Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia. Crit Care: 2011; 15 2 R79
61. Anderson D. J.; Engemann J. J.; Harrell L. J.; Carmeli Y.; Reller L. B.; Kaye K. S. Predictors of mortality in patients with bloodstream infection due to ceftazidime-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother: 2006; 50 5 1715 1720
62. Lodise T. P. Jr, Patel N.; Kwa A.; et al. Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother: 2007; 51 10 3510 3515
63. Mathevon T.; Souweine B.; Traoré O.; Aublet B.; Caillaud D. ICU-acquired nosocomial infection: impact of delay of adequate antibiotic treatment. Scand J Infect Dis: 2002; 34 11 831 835
64. Morrell M.; Fraser V. J.; Kollef M. H. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother: 2005; 49 9 3640 3645
65. Zahar J-R, Azoulay E.; Klement E.; et al. Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure. Intensive Care Med: 2001; 27 3 513 520
66. Gaieski D. F.; Mikkelsen M. E.; Band R. A.; et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med: 2010; 38 4 1045 1053
67. Lueangarun S.; Leelarasamee A. Impact of inappropriate empiric antimicrobial therapy on mortality of septic patients with bacteremia: a retrospective study. Interdiscip Perspect Infect Dis: 2012; 2012 2012 765205
68. Lin M. Y.; Weinstein R. A.; Hota B. Delay of active antimicrobial therapy and mortality among patients with bacteremia: impact of severe neutropenia. Antimicrob Agents Chemother: 2008; 52 9 3188 3194
69. Corona A.; Bertolini G.; Lipman J.; Wilson A. P.; Singer M. Antibiotic use and impact on outcome from bacteraemic critical illness: the Bacteraemia Study in Intensive Care (BASIC). J Antimicrob Chemother: 2010; 65 6 1276 1285
70. Silber S. H.; Garrett C.; Singh R.; et al. Early administration of antibiotics does not shorten time to clinical stability in patients with moderate-to-severe community-acquired pneumonia. Chest: 2003; 124 5 1798 1804
71. Kaasch A. J.; Rieg S.; Kuetscher J.; et al. preSABATO Study Group. Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study. Infection: 2013; 41 5 979 985
72. Kumar A.; Roberts D.; Wood K. E.; et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med: 2006; 34 6 1589 1596
73. Lodise T. P.; McKinnon P. S.; Swiderski L.; Rybak M. J. Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis: 2003; 36 11 1418 1423
74. Menéndez R.; Torres A.; Reyes S.; et al. Initial management of pneumonia and sepsis: factors associated with improved outcome. Eur Respir J: 2012; 39 1 156 162
75. Iregui M.; Ward S.; Sherman G.; Fraser V. J.; Kollef M. H. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest: 2002; 122 1 262 268
76. Aronin S. I.; Peduzzi P.; Quagliarello V. J. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med: 1998; 129 11 862 869
77. Ferrer R.; Artigas A.; Suarez D.; et al. Edusepsis Study Group. Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med: 2009; 180 9 861 866
78. Dellinger R. P.; Levy M. M.; Carlet J. M.; et al. International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med: 2008; 36 1 296 327
79. Taccone F. S.; Laterre P-F, Dugernier T.; et al. Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care: 2010; 14 4 R126
80. Chelluri L.; Jastremski M. S. Inadequacy of standard aminoglycoside loading doses in acutely ill patients. Crit Care Med: 1987; 15 12 1143 1145
81. Ocampos-Martinez E.; Penaccini L.; Scolletta S.; et al. Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients. Int J Antimicrob Agents: 2012; 39 4 332 337
82. Varghese J. M.; Roberts J. A.; Lipman J. Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock. Crit Care Clin: 2011; 27 1 19 34
83. Pea F.; Viale P. Bench-to-bedside review: Appropriate antibiotic therapy in severe sepsis and septic shock-does the dose matter? Crit Care: 2009; 13 3 214
84. Calandra T.; Glauser M. P. Immunocompromised animal models for the study of antibiotic combinations. Am J Med: 1986; 80 (5C): 45 52
85. Finberg R. W.; Moellering R. C.; Tally F. P.; et al. The importance of bactericidal drugs: future directions in infectious disease. Clin Infect Dis: 2004; 39 9 1314 1320
86. Pankey G. A.; Sabath L. D. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections. Clin Infect Dis: 2004; 38 6 864 870
87. Lepper M. H.; Dowling H. F.; MH L. Treatment of pneumococcic meningitis with penicillin compared with penicillin plus aureomycin; studies including observations on an apparent antagonism between penicillin and aureomycin. AMA Arch Intern Med: 1951; 88 4 489 494
88. Weinstein M. P.; Stratton C. W.; Ackley A.; et al. Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis. Am J Med: 1985; 78 2 262 269
89. Mylonakis E.; Calderwood S. B. Infective endocarditis in adults. N Engl J Med: 2001; 345 18 1318 1330
90. Weinstein M. P.; Stratton C. W.; Hawley H. B.; Ackley A.; Reller L. B. Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis. Am J Med: 1987; 83 2 218 222
91. Sculier J. P.; Klastersky J. Significance of serum bactericidal activity in gram-negative bacillary bacteremia in patients with and without granulocytopenia. Am J Med: 1984; 76 3 429 435
92. Small P. M.; Chambers H. F. Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother: 1990; 34 6 1227 1231
93. Khatib R.; Saeed S.; Sharma M.; Riederer K.; Fakih M. G.; Johnson L. B. Impact of initial antibiotic choice and delayed appropriate treatment on the outcome of Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis: 2006; 25 3 181 185
94. Kim S-H, Kim K-H, Kim H-B.; et al. Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia. Antimicrob Agents Chemother: 2008; 52 1 192 197
95. Rubinstein E.; Cammarata S.; Oliphant T.; Wunderink R.; Linezolid Nosocomial Pneumonia Study Group. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis: 2001; 32 3 402 412
96. Fagon J.; Patrick H.; Haas D. W.; et al. Nosocomial Pneumonia Group. Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Am J Respir Crit Care Med: 2000; 161 3, Pt 1 753 762
97. Fowler V. G. Jr, Boucher H. W.; Corey G. R.; et al. S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med: 2006; 355 7 653 665
98. McKinnon P. S.; Paladino J. A.; Schentag J. J. Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections. Int J Antimicrob Agents: 2008; 31 4 345 351
99. Crandon J. L.; Bulik C. C.; Kuti J. L.; Nicolau D. P. Clinical pharmacodynamics of cefepime in patients infected with Pseudomonas aeruginosa. Antimicrob Agents Chemother: 2010; 54 3 1111 1116
100. Chytra I.; Stepan M.; Benes J.; et al. Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial. Crit Care: 2012; 16 3 R113
101. Lorente L.; Jiménez A.; Martín M. M.; Iribarren J. L.; Jiménez J. J.; Mora M. L. Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents: 2009; 33 5 464 468
102. Lorente L.; Jiménez A.; Palmero S.; et al. Comparison of clinical cure rates in adults with ventilator-associated pneumonia treated with intravenous ceftazidime administered by continuous or intermittent infusion: a retrospective, nonrandomized, open-label, historical chart review. Clin Ther: 2007; 29 11 2433 2439
103. Lorente L.; Lorenzo L.; Martín M. M.; Jiménez A.; Mora M. L. Meropenem by continuous versus intermittent infusion in ventilator-associated pneumonia due to gram-negative bacilli. Ann Pharmacother: 2006; 40 2 219 223
104. Lodise T. P. Jr, Lomaestro B.; Drusano G. L. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis: 2007; 44 3 357 363
105. Kasiakou S. K.; Sermaides G. J.; Michalopoulos A.; Soteriades E. S.; Falagas M. E. Continuous versus intermittent intravenous administration of antibiotics: a meta-analysis of randomised controlled trials. Lancet Infect Dis: 2005; 5 9 581 589
106. Roberts J. A.; Webb S.; Paterson D.; Ho K. M.; Lipman J. A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med: 2009; 37 6 2071 2078
107. Scaglione F.; Mouton J. W.; Mattina R.; Fraschini F. Pharmacodynamics of levofloxacin and ciprofloxacin in a murine pneumonia model: peak concentration/MIC versus area under the curve/MIC ratios. Antimicrob Agents Chemother: 2003; 47 9 2749 2755
108. Winterboer T. M.; Lecci K. A.; Olsen K. M. Continuing education: alternative approaches to optimizing antimicrobial pharmacodynamics in critically ill patients. J Pharm Pract: 2010; 23 1 6 18
109. Forrest A.; Nix D. E.; Ballow C. H.; Goss T. F.; Birmingham M. C.; Schentag J. J. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother: 1993; 37 5 1073 1081
110. Moore R. D.; Smith C. R.; Lietman P. S. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. Am J Med: 1984; 77 4 657 662
111. Moore R. D.; Smith C. R.; Lietman P. S. The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis: 1984; 149 3 443 448
112. Moore R. D.; Lietman P. S.; Smith C. R. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis: 1987; 155 1 93 99
113. Kullar R.; Davis S. L.; Levine D. P.; Rybak M. J. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis: 2011; 52 8 975 981
114. Moise-Broder P. A.; Forrest A.; Birmingham M. C.; Schentag J. J. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet: 2004; 43 13 925 942
115. Zelenitsky S.; Rubinstein E.; Ariano R.; et al. Cooperative Antimicrobial Therapy of Septic Shock-CATSS Database Research Group. Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock. Int J Antimicrob Agents: 2013; 41 3 255 260
116. Chow J. W.; Yu V. L. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents: 1999; 11 1 7 12 A
117. Micek S. T.; Welch E. C.; Khan J.; et al. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis. Antimicrob Agents Chemother: 2010; 54 5 1742 1748
118. Giamarellou H.; Zissis N. P.; Tagari G.; Bouzos J. In vitro synergistic activities of aminoglycosides and new beta-lactams against multiresistant Pseudomonas aeruginosa. Antimicrob Agents Chemother: 1984; 25 4 534 536
119. Klastersky J.; Zinner S. H. Synergistic combinations of antibiotics in gram-negative bacillary infections. Rev Infect Dis: 1982; 4 2 294 301
120. Mouton J. W. Combination therapy as a tool to prevent emergence of bacterial resistance. Infection: 1999; 27 02 S24 S28
121. Anderson E. T.; Young L. S.; Hewitt W. L. Antimicrobial synergism in the therapy of gram-negative rod bacteremia. Chemotherapy: 1978; 24 1 45 54
122. Giamarellou H. Aminoglycosides plus beta-lactams against gram-negative organisms. Evaluation of in vitro synergy and chemical interactions. Am J Med: 1986; 80 (6B): 126 137
123. Kluge R. M.; Standiford H. C.; Tatem B.; et al. Comparative activity of tobramycin, amikacin, and gentamicin alone and with carbenicillin against Pseudomonas aeruginosa. Antimicrob Agents Chemother: 1974; 6 4 442 446 A
124. Neu H. C. Synergy and antagonism of fluoroquinolones with other classes of antimicrobial agents. Drugs: 1993; 45 03 54 58
125. Pohlman J. K.; Knapp C. C.; Ludwig M. D.; Washington J. A. Timed killing kinetic studies of the interaction between ciprofloxacin and β-lactams against gram-negative bacilli. Diagn Microbiol Infect Dis: 1996; 26 1 29 33
126. MacGowan A. R.; Bowker K.; Bedford K. A.; Holt H. A.; Reeves D. S. Synergy testing of macrolide combinations using the chequerboard technique. J Antimicrob Chemother: 1993; 32 6 913 915
127. Manian F. A.; Meyer L.; Jenne J.; Owen A.; Taff T. Loss of antimicrobial susceptibility in aerobic gram-negative bacilli repeatedly isolated from patients in intensive-care units. Infect Control Hosp Epidemiol: 1996; 17 4 222 226
128. Safdar N.; Handelsman J.; Maki D. G. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis: 2004; 4 8 519 527
129. Marcus R.; Paul M.; Elphick H.; Leibovici L. Clinical implications of β-lactam-aminoglycoside synergism: systematic review of randomised trials. Int J Antimicrob Agents: 2011; 37 6 491 503
130. Paul M.; Benuri-Silbiger I.; Soares-Weiser K.; Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ: 2004; 328 7441 668
131. Paul M.; Silbiger I.; Grozinsky S.; Soares-Weiser K.; Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev: 2006; 1 CD003344
132. Paul M.; Lador A.; Grozinsky-Glasberg S.; Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev: 2014; 1 CD003344
133. Paul M.; Soares-Weiser K.; Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. BMJ: 2003; 326 7399 1111
134. Waterer G. W.; Somes G. W.; Wunderink R. G. Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med: 2001; 161 15 1837 1842
135. Baddour L. M.; Yu V. L.; Klugman K. P.; et al. International Pneumococcal Study Group. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med: 2004; 170 4 440 444
136. Rodríguez A.; Mendia A.; Sirvent J-M.; et al. CAPUCI Study Group. Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock. Crit Care Med: 2007; 35 6 1493 1498
137. Hilf M.; Yu V. L.; Sharp J.; Zuravleff J. J.; Korvick J. A.; Muder R. R. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med: 1989; 87 5 540 546
138. Korvick J. A.; Bryan C. S.; Farber B.; et al. Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. Antimicrob Agents Chemother: 1992; 36 12 2639 2644 A
139. Kumar A.; Safdar N.; Kethireddy S.; Chateau D. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study. Crit Care Med: 2010; 38 8 1651 1664
140. Abad C. L.; Kumar A.; Safdar N. Antimicrobial therapy of sepsis and septic shock-when are two drugs better than one? Crit Care Clin: 2011; 27 2 e1 e27
141. Brunkhorst F. M.; Oppert M.; Marx G.; et al. German Study Group Competence Network Sepsis (SepNet). Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA: 2012; 307 22 2390 2399
142. Delannoy P-Y, Boussekey N.; Devos P.; et al. Impact of combination therapy with aminoglycosides on the outcome of ICU-acquired bacteraemias. Eur J Clin Microbiol Infect Dis: 2012; 31 9 2293 2299