Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study
Tóm tắt
Antibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance. To assess a carbapenem-based de-escalating strategy in nosocomial pneumonia (NP), a prospective observational study was conducted in critically ill patients with NP treated empirically with imipenem ± aminoglycoside/glycopeptide in 24 intensive care units of Spanish general hospitals. Overall, 244 patients were assessable (91% with late-onset NP). The primary outcome was therapeutic success 7–9 days post therapy. Microbial identification – based on cultures of tracheal aspirates in 82% of patients, cultures of protected specimen brush in 33%, and cultures of bronchoalveolar lavage in 4% – was only available for 131 (54%) patients. Initial antibiotics were inadequate for 23 (9%) patients. Of the remaining patients, antibiotics were streamlined in 56 (23%) patients and remained unchanged in 14 (6%) patients based on microbiology data, in 38 (16%) patients despite microbiology data favouring de-escalation, and in 113 (46%) patients due to unknown aetiology. Overall, de-escalation was implemented in only 23% of patients with potentially multiresistant pathogens, compared with 68% of patients with the remaining pathogens (P < 0.001). Response rates were 53% for patients continuously treated with imipenem-based regimens and 50% for the de-escalated patients. Higher Acute Physiology, Age, and Chronic Health Evaluation II scores were associated with greater mortality, whereas adequate empiric antibiotic therapy protected against fatal outcomes. No increase of superinfection rates caused by emerging pathogens was observed. The costs associated with de-escalation were mainly dependent on the duration of hospitalization. This study mainly highlights the current practice of a specific algorithm of de-escalation solely based on the available microbiological data, and highlights the barriers to using it more widely. In this setting, de-escalation was less likely to occur in the presence of potentially multiresistant pathogens. Prior antibiotic administration and the low use of bronchoscopic techniques may have influenced negatively the implementation of de-escalation. Optimization of de-escalation strategies for NP should rely on a correct choice of empiric antibiotics, on appropriate microbiological investigations, and on a balanced interpretation of microbiological and clinical data.
Tài liệu tham khảo
Rello J, Gallego M, Mariscal D, Sonora R, Valles J: The value of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med 1997, 156: 196-200.
Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH: Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002, 122: 262-268. 10.1378/chest.122.1.262
Luna CM, Vujacich P, Niederman MS, Vay C, Gherardi C, Matera J, Jolly EC: Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997, 111: 676-685.
Álvarez-Lerma F: Modification of empiric treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. Intensive Care Med 1996, 22: 387-394. 10.1007/BF01712153
Kollef MH, Sherman G, Ward S, Fraser VJ: Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999, 115: 462-474. 10.1378/chest.115.2.462
Kollef MH: Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 2000, 31: S131-S138. 10.1086/314079
Celis R, Torres A, Gatell JM, Almela M, Rodriguez-Roisin R, Agusti-Vidal A: Nosocomial pneumonia: a multivariate analysis of risk and prognosis. Chest 1988, 93: 318-324.
Torres A, Aznar R, Gatell JM, Jimenez P, Gonzalez J, Ferrer A, Celis R, Rodriguez-Roisin R: Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990, 142: 523-528.
Kollef MH, Ward S: The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest 1998, 113: 412-420.
Mathevon T, Souweine B, Traore O, Aublet B, Caillaud D: ICU-acquired nosocomial infection: impact of delay of adequate antibiotic treatment. Scand J Infect Dis 2002, 34: 831-835. 10.1080/0036554021000026934
Kollef MH: Appropriate empirical antibacterial therapy for nosocomial infections: getting it right the first time. Drugs 2003, 63: 2157-2168. 10.2165/00003495-200363200-00001
Hoffken G, Niederman MS: Nosocomial pneumonia: the importance of a de-escalation strategy for antibiotic treatment of pneumonia in the ICU. Chest 2002, 122: 2183-2196. 10.1378/chest.122.6.2183
Rello J, Vidaur L, Sandiumenge A, Rodriguez A, Gualis B, Boque C, Diaz E: De-escalation therapy in ventilator-associated pneumonia. Crit Care Med 2004, 32: 2183-2190.
Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM: CDC definitions of nosocomial infections. Am J Infect Control 1988, 16: 128-140. 10.1016/0196-6553(88)90053-3
Kollef MH, Kollef KE: Antibiotic utilization and outcomes for patients with clinically suspected ventilator-associated pneumonia and negative quantitative BAL culture results. Chest 2005, 128: 2706-2713. 10.1378/chest.128.4.2706
Carmeli Y, Troillet N, Eliopoulos GM, Samore MH: Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 1999, 43: 1379-1382.
Lepper PM, Grusa E, Reichl H, Hogel J, Trautmann M: Consumption of imipenem correlates with beta-lactam resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother 2002, 46: 2920-2925. 10.1128/AAC.46.9.2920-2925.2002
Aoun M, Crokaert F, Paesmans M, Autier P, Klastersky J: Imipenem versus targeted therapy in cancer patients. Int J Antimicrob Agents 1998, 10: 263-270. 10.1016/S0924-8579(98)00055-7
Namias N, Harvill S, Ball S, McKenney MG, Salomone JP, Sleeman D, Civetta JM: Empiric therapy of sepsis in the surgical intensive care unit with broad-spectrum antibiotics for 72 hours does not lead to the emergence of resistant bacteria. J Trauma 1998, 45: 887-891. 10.1097/00005373-199811000-00008
McGowan JE Jr: Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 1983, 5: 1033-1048.
Rahal JJ, Urban C, Horn D, Freeman K, Segal-Maurer S, Maurer J, Mariano N, Marks S, Burns JM, Dominick N, et al.: Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella . JAMA 1998, 280: 1233-1237. 10.1001/jama.280.14.1233
Fridkin SK, Edwards JR, Tenover FC, Gaynes RP, McGowan JE Jr: Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Project. National Nosocomial Infections Surveillance (NNIS) System Hospitals. Antimicrobial resistance prevalence rates in hospital antibiograms reflect prevalence rates among pathogens associated with hospital-acquired infections. Clin Infect Dis 2001, 33: 324-330. 10.1086/321893
Fridkin SK, Edwards JR, Courval JM, Hill H, Tenover FC, Lawton R, Gaynes RP, McGowan JE Jr: Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Project. National Nosocomial Infections Surveillance (NNIS) System Hospitals. The effect of vancomycin and third-generation cephalosporins on prevalence of vancomycin-resistant enterococci in 126 U.S. adult intensive care units. Ann Intern Med 2001, 135: 173-183.
Rello J, Sa-Borges M, Correa H, Leal SR, Baraibar J: Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am J Respir Crit Care Med 1999, 160: 608-613.
Álvarez-Lerma F, Insausti-Ordenana J, Jorda-Marcos R, Maravi-Poma E, Torres-Marti A, Nava J, Martinez-Pellus A, Palomar M, Barcenilla F: Efficacy and tolerability of piperacillin/tazobactam versus ceftazidime in association with amikacin for treating nosocomial pneumonia in intensive care patients: a prospective randomized multicenter trial. Intensive Care Med 2001, 27: 493-502. 10.1007/s001340000846