Нозокомиальная пневмония, связанная с искусственной вентиляцией легких: антибактериальная терапия короткими курсами

1. Kollef MH: Ventilator-associated pneumonia. A multivariate analysis. JAMA 1993; 270: 1965–70.
2. Vincent JL, Rello J, Marshall et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302: 2323–9.
3. American Thoracic Society Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388–416.
4. Rotstein C, Evans G, Born A et al. Clinical practice guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia in adults. Can J Infect Dis Med Microbiol 2008; 19: 19–53. 
5. Авдеев С.Н., Белобородов В.Б., Белоцерковский Б.З. и др. Нозокомиальная пневмония у взрослых (Национальные рекомендации). Под ред. А.Г.Чучалина, Б.Р.Гельфанда. Клин. микробиология и антимикроб. химиотерапия. 2009; 11 (2): 100–38. / Avdeev S.N., Beloborodov V.B., Belotserkovskiĭ B.Z. i dr. Nozokomialnaia pnevmoniia u vzroslykh (Natsionalnye rekomendatsii). Pod red. A.G.Chuchalina, B.R.Gelfanda. Klin. mikrobiologiia i antimikrob. khimioterapiia. 2009; 11 (2): 100–38. [in Russian]
6. Barlow M, Hall BG. Phylogenetic analysis shows that the OXA beta- lactamase genes have been on plasmids for millions of years. J Mol Evol 2002; 55: 314–21. 
7. D'Costa VM, King CE, Kalan L et al. Antibiotic resistance is ancient. Nature 2011; 477: 457–61.
8. Armand-Lefevre L, Angebault C, Barbier F et al. Emergence of imipenem-resistant Gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother 2013; 57: 1488–95.
9. Bell BG, Schellevis F, Stobberingh E et al. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 2014; 14: 13.
10. Meyer E, Gastmeier P, Deja M, Schwab F. Antibiotic consumption and resistance: data from Europe and Germany. Int J Med Microbiol 2013; 303: 388–95. 
11. Goossens H. Antibiotic consumption and link to resistance. Clin Microbiol Infect 2009; 15 (Suppl. 3): 12–5. 
12. Goossens H, Ferech M, Vander SR, Elseviers M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005; 365: 579–87. 
13. Laxminarayan R, Duse A, Wattal C et al. Antibiotic resistance – the need for global solutions. Lancet Infect Dis 2013; 13: 1057–98. 
14. Garcia-Migura L, Hendriksen RS, Fraile L, Aarestrup FM. Antimicrobial resistance of zoonotic and commensal bacteria in Europe: the missing link between consumption and resistance in veterinary medicine. Vet Microbiol 2014; 170: 1–9.
15. Malhotra-Kumar S, Lammens C, Coenen S et al. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 2007; 369: 482–90.
16. Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clin Infect Dis 2003; 36: S11–23. 
17. Rodriguez-Rojas A, Rodriguez-Beltran J, Couce A, Blazquez J. Antibiotics and antibiotic resistance: a bitter fight against evolution. Int J Med Microbiol 2013; 303: 293–7. 
18. Paramythiotou E, Lucet JC, Timsit JF et al. Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomonal activity. Clin Infect Dis 2004; 38: 670–7. 
19. Carmeli Y, Lidji SK, Shabtai E et al. The effects of group 1 versus group 2 carbapenems on imipenem-resistant Pseudomonas aeruginosa: an ecological study. Diagn Microbiol Infect Dis 2011; 70: 367–72. 
20. 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. 
21. Patel N, Harrington S, Dihmess A et al. Clinical epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae. J Antimicrob Chemother 2011; 66: 1600–8. 
22. Kritsotakis EI, Tsioutis C, Roumbelaki M et al. Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase- producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study. J Antimicrob Chemother 2011; 66: 1383–91. 
23. 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: 251–8. 
24. Ferrer R, Martin-Loeches I, Phillips G et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014; 42: 1749–55. 
25. Paterson DL. “Collateral damage” from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis 2004; 38 (Suppl. 4): S341–5.
26. Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 2005; 18: 657–86. 
27. Rodriguez-Bano J, Navarro MD, Retamar P et al. Beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis 2012; 54: 167–74. 
28. Tamma PD, Han JH, Rock C et al. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum beta-lactamase bacteremia. Clin Infect Dis 2015; 60: 1319–25. 
29. Harris PN, Tambyah PA, Paterson DL. Beta-lactam and beta-lactamase inhibitor combinations in the treatment of extended-spectrum beta- lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infect Dis 2015; 15: 475–85. 
30. Lee NY, Lee CC, Huang WH et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended- spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 2013; 56: 488–95. 
31. Luyt CE, Aubry A, Lu Q et al. Imipenem, Meropenem, or Doripenem To Treat Patients with Pseudomonas aeruginosa Ventilator-Associated Pneumonia. Antimicrob Agents Chemother 2014; 58 (3): 1372–80.
32. Jones RN, Huynh HK, Biedenbach DJ. Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother 2004; 48: 3136–40.
33. Jones RN, Sader HS, Fritsche TR. Comparativeactivityofdoripenem and three other carbapenems tested against Gram-negative bacilli with various beta-lactamase resistance mechanisms. Diagn Microbiol Infect Dis 2005; 52: 71–4. 
34. Sakyo S, Tomita H, Tanimoto K et al. Potency of carbapenems for the prevention of carbapenem-resistant mutants of Pseudomonas aeruginosa: the high potency of a new carbapenem doripenem. J Antibiot (Tokyo) 2006; 59: 220–8.
35. Mushtaq S, Ge Y, Livermore DM. Doripenem versus Pseudomonas aeruginosa in vitro: activity against characterized isolates, mutants, and transconjugants and resistance selection potential. Antimicrob Agents Chemother 2004; 48: 3086–92.
36. Chastre J, Wunderink R, Prokocimer P et al. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med 2008; 36: 1089–96.
37. Réa-Neto A, Niederman M, Lobo SM et al. Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open-label, multicenter study. Curr Med Res Opin 2008; 24: 2113–26.
38. Chastre J, Wolff M, Fagon JY et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator- associated, pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588–98.
39. Kollef M, Chastre J, Clavel M et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care 2012; 16: R218.
40. Drusano GL, Lodise TP, Melnick D et al. Meropenem penetration into epithelial lining fluid in mice and humans and delineation of exposure targets. Antimicrob Agents Chemother 2011; 55: 3406–12.
41. Crandon JL, Ariano RE, Zelenitsky SA et al. Optimization of meropenem dosage in the critically ill population based on renal function. Intensive Care Med 2011; 37: 632–8.
42. Ibrahim EH, Ward S, Sherman G et al. Experience with a clinical guideline for the treatment of ventilator-associated pneumonia. Crit Care Med 2001; 29: 1109–15.
43. Micek ST, Ward S, Fraser VJ, Kollef MH. A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Chest 2004; 125: 1791–9.
44. Singh N, Rogers P, Atwood CW et al. 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: 505–11.
45. Bouadma L, Luyt CE, Tubach F et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375: 463–74.
46. Stolz D, Smyrnios N, Eggimann P et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 2009; 34: 1364–75.
47. Hedrick TL, McElearney ST, Smith RL et al. Duration of antibiotic therapy for ventilator-associated pneumonia caused by non-fermentative gram-negative bacilli. Surg Infect 2007; 8: 589–97. 
48. Kollef KE, Schramm GE, Wills AR et al. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest 2008; 134: 281–7. 
49. Florescu DF, Qiu F, McCartan MA et al. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis 2012; 54: 670–80.
50. Freire AT, Melnyk V, Kim MJ et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 2010; 68: 140–51. 
51. Neuner E, Ritchie D, Micek S. New antibiotics for healthcare associated pneumonia. Semin Respir Crit Care Med 2009; 30: 92–101.
52. Tamma PD, Putcha N, Suh YD et al. Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials. BMC Infect Dis 2011; 11: 181.
53. Roberts J, Webb S, Paterson D et al. A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med 2009; 37: 2071–8. 
54. Justo J, Gotfried MH, Deyo K et al. Doripenem intrapulmonary pharmacokinetics in healthy adult subjects. Proceedings of the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, 17-20 September 2011, Chicago, Illinois.
55. Roberts JA, Kirkpatrick CM, Roberts MS et al. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 2009; 64: 142–50.
56. Bulitta JB, Landersdorfer CB, Forrest A et al. Relevance of pharmacokinetic and pharmacodynamic modelling to clinical care of critically ill patients. Curr Pharm Biotechnol 2011; 12: 2044–61.
57. Goncalves-Pereira J, Povoa P. Antibiotics in critically ill patients- a systematic review of the pharmacokinetics of beta-lactams. Crit Care 2011; 15: R206.
58. Udy A, Roberts J, Lipman J. Implications of augmented renal clearance in critically ill patients. Nat Rev Nephrol 2011; 7: 539–43.
59. Udy AA, Varghese JM, Altukroni M et al. Subtherapeutc initial β-lactam concentrations in select critically ill patients. Association between augmented renal clearance and low trough drug concentrations. Chest 2012; 142: 30–9.

________________________________________________

1. Kollef MH: Ventilator-associated pneumonia. A multivariate analysis. JAMA 1993; 270: 1965–70.
2. Vincent JL, Rello J, Marshall et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302: 2323–9.
3. American Thoracic Society Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388–416.
4. Rotstein C, Evans G, Born A et al. Clinical practice guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia in adults. Can J Infect Dis Med Microbiol 2008; 19: 19–53. 
5. Avdeev S.N., Beloborodov V.B., Belotserkovskiĭ B.Z. i dr. Nozokomialnaia pnevmoniia u vzroslykh (Natsionalnye rekomendatsii). Pod red. A.G.Chuchalina, B.R.Gelfanda. Klin. mikrobiologiia i antimikrob. khimioterapiia. 2009; 11 (2): 100–38. [in Russian]
6. Barlow M, Hall BG. Phylogenetic analysis shows that the OXA beta- lactamase genes have been on plasmids for millions of years. J Mol Evol 2002; 55: 314–21. 
7. D'Costa VM, King CE, Kalan L et al. Antibiotic resistance is ancient. Nature 2011; 477: 457–61.
8. Armand-Lefevre L, Angebault C, Barbier F et al. Emergence of imipenem-resistant Gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother 2013; 57: 1488–95.
9. Bell BG, Schellevis F, Stobberingh E et al. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis 2014; 14: 13.
10. Meyer E, Gastmeier P, Deja M, Schwab F. Antibiotic consumption and resistance: data from Europe and Germany. Int J Med Microbiol 2013; 303: 388–95. 
11. Goossens H. Antibiotic consumption and link to resistance. Clin Microbiol Infect 2009; 15 (Suppl. 3): 12–5. 
12. Goossens H, Ferech M, Vander SR, Elseviers M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005; 365: 579–87. 
13. Laxminarayan R, Duse A, Wattal C et al. Antibiotic resistance – the need for global solutions. Lancet Infect Dis 2013; 13: 1057–98. 
14. Garcia-Migura L, Hendriksen RS, Fraile L, Aarestrup FM. Antimicrobial resistance of zoonotic and commensal bacteria in Europe: the missing link between consumption and resistance in veterinary medicine. Vet Microbiol 2014; 170: 1–9.
15. Malhotra-Kumar S, Lammens C, Coenen S et al. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 2007; 369: 482–90.
16. Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clin Infect Dis 2003; 36: S11–23. 
17. Rodriguez-Rojas A, Rodriguez-Beltran J, Couce A, Blazquez J. Antibiotics and antibiotic resistance: a bitter fight against evolution. Int J Med Microbiol 2013; 303: 293–7. 
18. Paramythiotou E, Lucet JC, Timsit JF et al. Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomonal activity. Clin Infect Dis 2004; 38: 670–7. 
19. Carmeli Y, Lidji SK, Shabtai E et al. The effects of group 1 versus group 2 carbapenems on imipenem-resistant Pseudomonas aeruginosa: an ecological study. Diagn Microbiol Infect Dis 2011; 70: 367–72. 
20. 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. 
21. Patel N, Harrington S, Dihmess A et al. Clinical epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae. J Antimicrob Chemother 2011; 66: 1600–8. 
22. Kritsotakis EI, Tsioutis C, Roumbelaki M et al. Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase- producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case-control study. J Antimicrob Chemother 2011; 66: 1383–91. 
23. 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: 251–8. 
24. Ferrer R, Martin-Loeches I, Phillips G et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014; 42: 1749–55. 
25. Paterson DL. “Collateral damage” from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis 2004; 38 (Suppl. 4): S341–5.
26. Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 2005; 18: 657–86. 
27. Rodriguez-Bano J, Navarro MD, Retamar P et al. Beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis 2012; 54: 167–74. 
28. Tamma PD, Han JH, Rock C et al. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum beta-lactamase bacteremia. Clin Infect Dis 2015; 60: 1319–25. 
29. Harris PN, Tambyah PA, Paterson DL. Beta-lactam and beta-lactamase inhibitor combinations in the treatment of extended-spectrum beta- lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infect Dis 2015; 15: 475–85. 
30. Lee NY, Lee CC, Huang WH et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended- spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 2013; 56: 488–95. 
31. Luyt CE, Aubry A, Lu Q et al. Imipenem, Meropenem, or Doripenem To Treat Patients with Pseudomonas aeruginosa Ventilator-Associated Pneumonia. Antimicrob Agents Chemother 2014; 58 (3): 1372–80.
32. Jones RN, Huynh HK, Biedenbach DJ. Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother 2004; 48: 3136–40.
33. Jones RN, Sader HS, Fritsche TR. Comparativeactivityofdoripenem and three other carbapenems tested against Gram-negative bacilli with various beta-lactamase resistance mechanisms. Diagn Microbiol Infect Dis 2005; 52: 71–4. 
34. Sakyo S, Tomita H, Tanimoto K et al. Potency of carbapenems for the prevention of carbapenem-resistant mutants of Pseudomonas aeruginosa: the high potency of a new carbapenem doripenem. J Antibiot (Tokyo) 2006; 59: 220–8.
35. Mushtaq S, Ge Y, Livermore DM. Doripenem versus Pseudomonas aeruginosa in vitro: activity against characterized isolates, mutants, and transconjugants and resistance selection potential. Antimicrob Agents Chemother 2004; 48: 3086–92.
36. Chastre J, Wunderink R, Prokocimer P et al. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med 2008; 36: 1089–96.
37. Réa-Neto A, Niederman M, Lobo SM et al. Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open-label, multicenter study. Curr Med Res Opin 2008; 24: 2113–26.
38. Chastre J, Wolff M, Fagon JY et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator- associated, pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588–98.
39. Kollef M, Chastre J, Clavel M et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care 2012; 16: R218.
40. Drusano GL, Lodise TP, Melnick D et al. Meropenem penetration into epithelial lining fluid in mice and humans and delineation of exposure targets. Antimicrob Agents Chemother 2011; 55: 3406–12.
41. Crandon JL, Ariano RE, Zelenitsky SA et al. Optimization of meropenem dosage in the critically ill population based on renal function. Intensive Care Med 2011; 37: 632–8.
42. Ibrahim EH, Ward S, Sherman G et al. Experience with a clinical guideline for the treatment of ventilator-associated pneumonia. Crit Care Med 2001; 29: 1109–15.
43. Micek ST, Ward S, Fraser VJ, Kollef MH. A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Chest 2004; 125: 1791–9.
44. Singh N, Rogers P, Atwood CW et al. 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: 505–11.
45. Bouadma L, Luyt CE, Tubach F et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375: 463–74.
46. Stolz D, Smyrnios N, Eggimann P et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 2009; 34: 1364–75.
47. Hedrick TL, McElearney ST, Smith RL et al. Duration of antibiotic therapy for ventilator-associated pneumonia caused by non-fermentative gram-negative bacilli. Surg Infect 2007; 8: 589–97. 
48. Kollef KE, Schramm GE, Wills AR et al. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest 2008; 134: 281–7. 
49. Florescu DF, Qiu F, McCartan MA et al. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis 2012; 54: 670–80.
50. Freire AT, Melnyk V, Kim MJ et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 2010; 68: 140–51. 
51. Neuner E, Ritchie D, Micek S. New antibiotics for healthcare associated pneumonia. Semin Respir Crit Care Med 2009; 30: 92–101.
52. Tamma PD, Putcha N, Suh YD et al. Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials. BMC Infect Dis 2011; 11: 181.
53. Roberts J, Webb S, Paterson D et al. A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med 2009; 37: 2071–8. 
54. Justo J, Gotfried MH, Deyo K et al. Doripenem intrapulmonary pharmacokinetics in healthy adult subjects. Proceedings of the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, 17-20 September 2011, Chicago, Illinois.
55. Roberts JA, Kirkpatrick CM, Roberts MS et al. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 2009; 64: 142–50.
56. Bulitta JB, Landersdorfer CB, Forrest A et al. Relevance of pharmacokinetic and pharmacodynamic modelling to clinical care of critically ill patients. Curr Pharm Biotechnol 2011; 12: 2044–61.
57. Goncalves-Pereira J, Povoa P. Antibiotics in critically ill patients- a systematic review of the pharmacokinetics of beta-lactams. Crit Care 2011; 15: R206.
58. Udy A, Roberts J, Lipman J. Implications of augmented renal clearance in critically ill patients. Nat Rev Nephrol 2011; 7: 539–43.
59. Udy AA, Varghese JM, Altukroni M et al. Subtherapeutc initial β-lactam concentrations in select critically ill patients. Association between augmented renal clearance and low trough drug concentrations. Chest 2012; 142: 30–9.

В.Б.Белобородов*, В.А.Синикин 

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, 
ул. Баррикадная, д. 2/1
*vb_beloborodov@mail.ru

________________________________________________

V.B.Beloborodov*, V.A.Sinikin

Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, 
ul. Barrikadnaia, d. 2/1
*vb_beloborodov@mail.ru