645
Views
19
CrossRef citations to date
0
Altmetric
Review

Management of ventilator-associated pneumonia (VAP) caused by resistant gram-negative bacteria: which is the best strategy to treat?

, ORCID Icon &
Pages 787-798 | Received 18 Jan 2019, Accepted 12 Jun 2019, Published online: 24 Jun 2019

References

  • Craven DE, Hudcova J, Lei Y: Diagnosis of ventilator-associated respiratory infections (VARI): microbiologic clues for tracheobronchitis (VAT) and pneumonia (VAP). Clin Chest Med. 2011; 32(3): 547–557.
  • Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of america and the american thoracic society. Clin Infect Dis. 2016;63:e61–e111.
  • Bouadma L, Sonneville R, Garrouste-Orgeas M, et al. Ventilator-associated events. Crit Care Med. 2015;43:1798–1806.
  • Rosenthal VD, Bijie H, Maki DG, et al. International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004–2009. Am J Infect Control. 2012;40:396–407.
  • Koulenti D, Tsigou E, Rello J. Nosocomial pneumonia in 27 ICUs in Europe: perspectives from the EU-VAP/CAP study. Eur J Clin Microbiol Infect Dis. 2017;36:1999–2006.
  • Asehnoune K, Seguin P, Allary J, et al. Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial. Lancet Respir Med. 2014;2:706–716.
  • Micek ST, Wunderink RG, Kollef MH, et al. An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance. Crit Care. 2015;19:219.
  • von Cube MK, Timsit J-F, Sommer H, et al. Relative risk and population-attributable fraction of ICU death caused by susceptible and resistant Pseudomonas aeruginosa ventilator-associated pneumonia: a competing risks approach to investigate the OUTCOMEREA database. Intensive Care Med. 2018;44:1177–1179.
  • Garnacho-Montero J, Ortiz-Leyba C, Fernández-Hinojosa E, et al. Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings. Intensive Care Med. 2005;31:649–655.
  • Melsen WG, Rovers MM, Koeman M, et al. Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies*. Crit Care Med. 2011;39:2736–2742.
  • Klompas M. Complications of mechanical ventilation — the CDC’s new surveillance paradigm. N Engl J Med. 2013;368:1472–1475.
  • Klompas M, Kleinman K, Murphy MV. Descriptive epidemiology and attributable morbidity of ventilator-associated events. Infect Control Hosp Epidemiol. 2014;35:502–510.
  • Peña-López Y, Pujol M, Campins M, et al. Assessing prediction accuracy for outcomes of ventilator-associated events and infections in critically ill children: a prospective cohort study. Clin Microbiol Infect. 2018;24:732–737.
  • Ramírez-Estrada S, Lagunes L, Peña-López Y, et al. Assessing predictive accuracy for outcomes of ventilator-associated events in an international cohort: the EUVAE study. Intensive Care Med. 2018;44:1212–1220.
  • Sandiumenge A, Rello J. Ventilator-associated pneumonia caused by ESKAPE organisms. Curr Opin Pulm Med. 2012;18:187–193.
  • Sligl WI, Dragan T, Smith SW. Nosocomial Gram-negative bacteremia in intensive care: epidemiology, antimicrobial susceptibilities, and outcomes. Int J Infect Dis. 2015;37:129–134.
  • McCarthy K. Pseudomonas aeruginosa: evolution of Antimicrobial Resistance and Implications for Therapy. Semin Respir Crit Care Med. 2015;36:044–055.
  • Magiorakos A-P, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–281.
  • Kadri SS, Adjemian J, Lai YL, et al. Difficult-to-treat resistance in Gram-negative bacteremia at 173 US Hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin Infect Dis. 2018;67:1803–1814.
  • Borgatta B, Gattarello S, Mazo CA, et al. The clinical significance of pneumonia in patients with respiratory specimens harbouring multidrug-resistant Pseudomonas aeruginosa: a 5-year retrospective study following 5667 patients in four general ICUs. Eur J Clin Microbiol Infect Dis. 2017;36:2155–2163.
  • Fernández-Barat L, Ferrer M, De Rosa F, et al. Intensive care unit-acquired pneumonia due to Pseudomonas aeruginosa with and without multidrug resistance. J Infect. 2017;74:142–152.
  • Hurley JC. World-wide variation in incidence of Acinetobacter associated ventilator associated pneumonia: a meta-regression. BMC Infect Dis. 2016;16:577.
  • Chastre J, Fagon J-Y. Ventilator-associated Pneumonia. Am J Respir Crit Care Med. 2002;165:867–903.
  • Pilmis B, Zahar J-R. Ventilator-associated pneumonia related to ESBL-producing gram negative bacilli. Ann Transl Med. 2018;6:424.
  • Sader HS, Farrell DJ, Flamm RK, et al. Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalised with pneumonia in US and European hospitals: results from the SENTRY antimicrobial surveillance program, 2009–2012. Int J Antimicrob Agents. 2014;43:328–334.
  • Tacconelli E, Cataldo MA, De Pascale G, et al. Prediction models to identify hospitalized patients at risk of being colonized or infected with multidrug-resistant Acinetobacter baumannii calcoaceticus complex. J Antimicrob Chemother. 2008;62:1130–1137.
  • Planquette B, Timsit J-F, Misset BY, et al. Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure. Am J Respir Crit Care Med. 2013;188:69–76.
  • Papadimitriou-Olivgeris M, Marangos M, Christofidou M, et al. Risk factors for infection and predictors of mortality among patients with KPC-producing Klebsiella pneumoniae bloodstream infections in the intensive care unit. Scand J Infect Dis. 2014;46:642–648.
  • Restrepo MI, Peterson J, Fernandez JF, et al. Comparison of the bacterial etiology of early-onset and late-onset ventilator-associated pneumonia in subjects enrolled in 2 large clinical studies. Respir Care. 2013;58:1220–1225.
  • Zilberberg M, Nathanson B, Sulham K, et al. Impact of inappropriate empiric treatment of acinetobacter baumannii pneumonia and sepsis on hospital mortality. Chest. 2016;150:114A.
  • Timsit J-F, Esaied W, Neuville M, et al. Update on ventilator-associated pneumonia. F1000Res. 2017;6:2061.
  • Aloush V, Navon-Venezia S, Seigman-Igra Y, et al. Multidrug-resistant pseudomonas aeruginosa: risk factors and clinical impact. Antimicrob Agents Chemother. 2006;50:43–48.
  • Playford EG, Craig JC, Iredell JR. Carbapenem-resistant Acinetobacter baumannii in intensive care unit patients: risk factors for acquisition, infection and their consequences. J Hosp Infect. 2007;65:204–211.
  • Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol. 2007;5:939–951.
  • Garnacho-Montero J, Amaya-Villar R. Multiresistant Acinetobacter baumannii infections: epidemiology and management. Curr Opin Infect Dis. 2010;23:332–339.
  • Vazquez Guillamet C, Kollef MH. Acinetobacter pneumonia: improving outcomes with early identification and appropriate therapy. Clin Infect Dis. 2018;67:1455–1462.
  • Levin AS, Levy CE, Manrique AEI, et al. Severe nosocomial infections with imipenem-resistant Acinetobacter baumannii treated with ampicillin/sulbactam. Int J Antimicrob Agents. 2003;21:58–62.
  • Wood GC, Hanes SD, Croce MA, et al. Comparison of ampicillin‐sulbactam and imipenem‐cilastatin for the treatment of acinetobacter ventilator‐associated pneumonia. Clin Infect Dis. 2002;34:1425–1430.
  • Betrosian AP, Frantzeskaki F, Xanthaki A, et al. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multidrug-resistant Acinetobacter baumannii. Scand J Infect Dis. 2007;39:38–43.
  • Chu H, Zhao L, Wang M, et al. Sulbactam-based therapy for Acinetobacter baumannii infection: a systematic review and meta-analysis. Brazilian J Infect Dis. 2013;17:389–394.
  • Alp E, Eren E, Elay G, et al. Efficacy of loading dose of colistin in Acinetobacter baumannii ventilator-associated pneumonia. Infez Med. 2017;25:311–319.
  • Khawcharoenporn T, Pruetpongpun N, Tiamsak P, et al. Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia. Int J Antimicrob Agents. 2014;43:378–382.
  • Makris D, Petinaki E, Tsolaki V, et al. Colistin versus colistin combined with ampicillin-sulbactam for multiresistant Acinetobacter baumannii ventilator-associated pneumonia treatment: an open-label prospective study. Indian J Crit Care Med. 2018;22:67.
  • Kempf M, Djouhri-Bouktab L, Brunel J-M, et al. Synergistic activity of sulbactam combined with colistin against colistin-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 2012;39:180–181.
  • Kengkla K, Kongpakwattana K, Saokaew S, et al. Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis. J Antimicrob Chemother. 2018;73:22–32.
  • Durante-Mangoni E, Signoriello G, Andini R, et al. 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. 2013;57:349–358.
  • Aydemir H, Akduman D, Piskin N, et al. Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia. Epidemiol Infect. 2013;141:1214–1222.
  • Paul M, Daikos GL, Durante-Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018;18:391–400.
  • Ramirez J, Dartois N, Gandjini H, et al. 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. 2013;57:1756–1762.
  • Chaari A, Pham T, Mnif B, et al. Colistin–tigecycline versus colistin–imipenem–cilastatin combinations for the treatment of Acinetobacter baumannii ventilator-acquired pneumonia: a prognosis study. Intensive Care Med. 2015;41:2018–2019.
  • Shen F, Han Q, Xie D, et al. Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs. Int J Infect Dis. 2015;39:25–33.
  • Prasad P, Sun J, Danner RL, et al. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis. 2012;54:1699–1709.
  • Lenhard JR, Smith NM, Bulman ZP, et al. High-dose ampicillin-sulbactam combinations combat polymyxin-resistant acinetobacter baumannii in a hollow-fiber infection model. Antimicrob Agents Chemother. 2017;61.
  • Micek ST, Wunderink RG, Kollef MH, et al. An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance. Crit Care. 2015;19:219.
  • Peña C, Gómez-Zorrilla S, Oriol I, et al. Impact of multidrug resistance on Pseudomonas aeruginosa ventilator-associated pneumonia outcome: predictors of early and crude mortality. Eur J Clin Microbiol Infect Dis. 2013;32:413–420.
  • Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum β-lactamase–producing enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant pseudomonas aeruginosa. Mayo Clin Proc. 2011;86:250–259.
  • Nakamura A, Miyake K, Misawa S, et al. Meropenem as predictive risk factor for isolation of multidrug-resistant Pseudomonas aeruginosa. J Hosp Infect. 2013;83:153–155.
  • Garnacho-Montero J, Sa-Borges M, Sole-Violan J, et al. Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med. 2007;35:1888–1895.
  • Carcas AJ, García-Satué JL, Zapater P, et al. Tobramycin penetration into epithelial lining fluid of patients with pneumonia. Clin Pharmacol Ther. 1999;65:245–250.
  • Mensa J, Barberán J, Soriano A, et al. Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: guidelines by the Spanish society of chemotherapy. Rev Esp Quimioter. 2018;31:78–100.
  • Slekovec C, Robert J, Trystram D, et al. Pseudomonas aeruginosa in French hospitals between 2001 and 2011: back to susceptibility. Eur J Clin Microbiol Infect Dis. 2014;33:1713–1717.
  • Heyland DK, Dodek P, Muscedere J, et al. Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med. 2008;36:737–744.
  • Borgatta B, Rello J. How to approach and treat VAP in ICU patients. BMC Infect Dis. 2014;14:211.
  • Torres A, Bauer TT, León-Gil C, et al. Treatment of severe nosocomial pneumonia: a prospective randomised comparison of intravenous ciprofloxacin with imipenem/cilastatin. Thorax. 2000;55:1033–1039.
  • Luyt C-E, Aubry A, Lu Q, et al. Imipenem, meropenem, or doripenem to treat patients with pseudomonas aeruginosa ventilator-associated pneumonia. Antimicrob Agents Chemother. 2014;58:1372–1380.
  • Kollef MH, 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.
  • Cannon JP, Lee TA, Clark NM, et al. The risk of seizures among the carbapenems: a meta-analysis. J Antimicrob Chemother. 2014;69:2043–2055.
  • Hoffman J, Trimble J, Brophy GM. Safety of imipenem/cilastatin in neurocritical care patients. Neurocrit Care. 2009;10:403–407.
  • Calandra G, Lydick E, Carrigan J, et al. Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin. Am J Med. 1988;84:911–918.
  • Vardakas KZ, Voulgaris GL, Maliaros A, et al. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018;18:108–120.
  • Lorente L, Lorenzo L, Martín MM, et al. Meropenem by continuous versus intermittent infusion in ventilator-associated pneumonia due to gram-negative bacilli. Ann Pharmacother. 2006;40:219–223.
  • Khawcharoenporn T, Chuncharunee A, Maluangnon C, et al. Active monotherapy and combination therapy for extensively drug-resistant Pseudomonas aeruginosa pneumonia. Int J Antimicrob Agents. 2018;52:828–834.
  • Furtado GHC, D’Azevedo PA, Santos AF, et al. Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa. Int J Antimicrob Agents. 2007;30:315–319.
  • Sorlí L, Luque S, Segura C, et al. Impact of colistin plasma levels on the clinical outcome of patients with infections caused by extremely drug-resistant Pseudomonas aeruginosa. BMC Infect Dis. 2017;17:11.
  • Rocco M, Montini L, Alessandri E, et al. Risk factors for acute kidney injury in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics: a retrospective cohort study. Crit Care. 2013;17:R174.
  • Drusano GL. Prevention of resistance: a goal for dose selection for antimicrobial agents. Clin Infect Dis. 2003;36:S42–S50.
  • Torres A, Zhong N, Pachl J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–295.
  • van Duin D, Bonomo RA. Ceftazidime/avibactam and ceftolozane/tazobactam: second-generation β-lactam/β-lactamase inhibitor combinations. Clin Infect Dis. Saravolatz LD, editor. 2016;63:234–241.
  • Wenzler E, Deraedt MF, Harrington AT, et al. Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamase-producing gram-negative pathogens. Diagn Microbiol Infect Dis. 2017;88:352–354.
  • Bruyère R, Vigneron C, Bador J, et al. Significance of prior digestive colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae in patients with ventilator-associated pneumonia. Crit Care Med. 2015;44:1.
  • Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, et al. Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clin Microbiol Rev. 2018 Feb 14;31(2).
  • Martinez JA, Cobos-Trigueros N, Soriano A, et al. Influence of empiric therapy with a -lactam alone or combined with an aminoglycoside on prognosis of bacteremia due to gram-negative microorganisms. Antimicrob Agents Chemother. 2010;54:3590–3596.
  • Harris PNA, Tambyah PA, Paterson DL. β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infect Dis. 2015;15:475–485.
  • Boucher A, Meybeck A, Patoz P, et al. Alternatives to carbapenems in ventilator-associated pneumonia due to ESBL-producing Enterobacteriaceae. J Infect. 2016;73:293–296.
  • Tamma PD, Han JH, Rock C, et al. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia. Clin Infect Dis. 2015;60:1319–1325.
  • Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin-tazobactam vs meropenem on 30 day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance. JAMA. 2018;320:984.
  • Shields RK, Potoski BA, Haidar G, et al. Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections: table 1. Clin Infect Dis. 2016;63:1615–1618.
  • Rojas LJ, Salim M, Cober E, et al. Colistin resistance in carbapenem-resistant Klebsiella pneumoniae: laboratory detection and impact on mortality. Clin Infect Dis. 2016;ciw805.
  • Falagas ME, Lourida P, Poulikakos P, et al. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence. Antimicrob Agents Chemother. 2014;58:654–663.
  • Qureshi ZA, Paterson DL, Potoski BA, et al. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother. 2012;56:2108–2113.
  • Tumbarello M, Trecarichi EM, De Rosa FG, et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother. 2015;70:2133–2143.
  • Tumbarello M, Viale P, Viscoli C, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55:943–950.
  • Bassetti M, Peghin M, Carnelutti A, et al. How should we treat HAP/VAP caused by carbapenemase-producing Enterobacteriaceae? Semin Respir Crit Care Med. 2017;38:301–310.
  • Giannella M, Trecarichi EM, Giacobbe DR, et al. Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection. Int J Antimicrob Agents. 2018;51:244–248.
  • Cancelli F, Oliva A, De Angelis M, et al. Role of double-carbapenem regimen in the treatment of infections due to carbapenemase producing carbapenem-resistant Enterobacteriaceae : a single-center, observational study. BioMed Res Int. 2018;2018:1–8.
  • Abdelsalam MFA, Abdalla MS, El-Abhar HSE-D. Prospective, comparative clinical study between high-dose colistin monotherapy and colistin–meropenem combination therapy for treatment of hospital-acquired pneumonia and ventilator-associated pneumonia caused by multidrug-resistant Klebsiella pneumoniae. J Glob Antimicrob Resist. 2018;15:127–135.
  • De Pascale G, Montini L, Pennisi M, et al. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care. 2014;18:R90.
  • Routsi C, Kokkoris S, Douka E, et al. High-dose tigecycline-associated alterations in coagulation parameters in critically ill patients with severe infections. Int J Antimicrob Agents. 2015;45:90–93.
  • Tzouvelekis LS, Markogiannakis A, Piperaki E, et al. Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect. 2014;20:862–872.
  • Gonzalez-Padilla M, Torre-Cisneros J, Rivera-Espinar F, et al. Gentamicin therapy for sepsis due to carbapenem-resistant and colistin-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2015;70:905–913.
  • Shields RK, Nguyen MH, Chen L, et al. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother. 2017;61.
  • van Duin D, Lok JJ, Earley M, et al. Colistin versus ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant Enterobacteriaceae. Clin Infect Dis. 2018;66:163–171.
  • Temkin E, Torre-Cisneros J, Beovic B, et al. Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms: a case series from the compassionate-use program. Antimicrob Agents Chemother. 2016; AAC:01964–16.
  • Alves J, Alp E, Koulenti D, et al. Nebulization of antimicrobial agents in mechanically ventilated adults in 2017: an international cross-sectional survey. Eur J Clin Microbiol Infect Dis. 2018;37:785–794.
  • Rello J, Solé-Lleonart C, Rouby -J-J, et al. Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European society of clinical microbiology and infectious diseases. Clin Microbiol Infect. 2017;23:629–639.
  • Solé-Lleonart C, Rouby -J-J, Blot S, et al. Nebulization of antiinfective agents in invasively mechanically ventilated adults. Anesthesiology. 2017;126:890–908.
  • Rello J, Rouby JJ, Sole-Lleonart C, et al. Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin Microbiol Infect. 2017;23:640–646.
  • Pulido MR, Moreno-Martínez P, González-Galán V, et al. Application of BioFire filmarray blood culture identification panel for rapid identification of the causative agents of ventilator-associated pneumonia. Clin Microbiol Infect. 2018 Nov;24(11):1213.e1-1213.e4.
  • Rello J, van Engelen TSR, Alp E, et al. Towards precision medicine in sepsis: a position paper from the European society of clinical microbiology and infectious diseases. Clin. Microbiol. Infect. 2018;24:1264–1272.
  • EUCAST. Comparative primate socioecology. Lee PC, editor. Eucast. Cambridge: Cambridge University Press; 1999.
  • van der Heijden IM, Levin AS, De Pedri EH, et al. Comparison of disc diffusion, Etest and broth microdilution for testing susceptibility of carbapenem-resistant P. aeruginosa to polymyxins. Ann Clin Microbiol Antimicrob. 2007;6:8.
  • Kulengowski B, Ribes JA, Burgess DS. Polymyxin B Etest® compared with gold-standard broth microdilution in carbapenem-resistant Enterobacteriaceae exhibiting a wide range of polymyxin B MICs. Clin Microbiol Infect. 2019;25:92–95.
  • Matuschek E, Åhman J, Webster C, et al. Antimicrobial susceptibility testing of colistin – evaluation of seven commercial MIC products against standard broth microdilution for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. Clin Microbiol Infect. 2018;24:865–870.
  • Chastre J, Wolff M, Fagon J-Y, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated Pneumonia in adults. JAMA. 2003;290:2588.
  • Vidaur L, Gualis B, Rodriguez A, et al. Clinical resolution in patients with suspicion of ventilator-associated pneumonia: A cohort study comparing patients with and without acute respiratory distress syndrome. Crit Care Med. 2005;33:1248–1253.
  • Zhanel GG, Chung P, Adam H, et al. Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs. 2014;74:31–51.
  • Farrell DJ, Sader HS, Flamm RK, et al. Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012). Int J Antimicrob Agents. 2014;43:533–539.
  • Poulakou G, Lagou S, Karageorgopoulos DE, et al. New treatments of multidrug-resistant Gram-negative ventilator-associated pneumonia. Ann Transl Med. 2018;6:423.
  • François B, Luyt C-E, Dugard A, et al. Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody fragment in mechanically ventilated patients colonized with Pseudomonas aeruginosa. Crit Care Med. 2012;40:2320–2326.
  • François B. New targets for new therapeutic approaches. Crit Care. 2014;18:669.
  • Capellier G, Mockly H, Charpentier C, et al. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. Spellberg B, editor. PLoS One. 2012;7:e41290.
  • Rello J, Ulldemolins M, Lisboa T, et al. Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia. Eur Respir J. 2011;37:1332–1339.
  • Rello J, Lisboa T, Koulenti D. Respiratory infections in patients undergoing mechanical ventilation. Lancet Respir Med. 2014;2:764–774.
  • Klompas M, Li L, Menchaca JT, et al. Ultra short course antibiotics for patients with suspected ventilator-associated pneumonia but minimal and stable ventilator settings. Clin Infect Dis. 2016;ciw870.
  • Vandana Kalwaje E, Rello J. Management of ventilator-associated pneumonia: need for a personalized approach. Expert Rev Anti Infect Ther. 2018;16:641–653.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.