Gruson Didier, Hilbert Gilles, Vargas Frederic, Valentino Ruddy, Bui Nam, Pereyre Sabine, Bebear Christianne, Bebear Cecile-Marie, Gbikpi-Benissan Georges
Intensive Care Unit 2, Department of Pulmonary and Critical Care Medicine, Bordeaux, France.
Crit Care Med. 2003 Jul;31(7):1908-14. doi: 10.1097/01.CCM.0000069729.06687.DE.
To evaluate the long-term effect of a program of rotating antibiotics on the incidence of ventilator-associated pneumonia and the susceptibilities of Gram-negative bacilli responsible for ventilator-associated pneumonia.
Prospective program for the surveillance of antibiotic susceptibilities of microorganisms responsible for ventilator-associated pneumonia.
Academic, university-based, medical intensive care unit (16 beds).
2,856 mechanically ventilated patients.
A new program of antibiotic use was introduced at the end of 1996 that involved the rotation of antibiotics in empirical and therapeutic use of the treatment of ventilator-associated pneumonia. The rotation concerned the beta-lactam and aminoglycoside classes, with a rotation interval of 1 month. The use of antibiotics was monitored monthly. No preference was given to any particular antibiotic. In a previous study, the period before the introduction of this protocol (1995-1996) was compared with the period 2 yrs after (1997-1998): The results indicated a decreased incidence of ventilator-associated pneumonia, a lower incidence of potentially resistant Gram-negative bacilli, and increased sensitivities of Gram-negative bacilli, especially Pseudomonas aeruginosa and Burkholderia cepacia. After 1998, we decided to continue a routine for this rotation. The long-term effect of this program was studied by comparing the incidence of Gram-negative bacilli responsible for ventilator-associated pneumonia and their susceptibilities obtained in a third period: 1999-2001. The long-term effect (5 yrs) of such a strategy-2-yr protocol period (1997-1998) and 3-yr routine period (1999-2001)-could be evaluated.
During the 7-yr study period, 2,856 patients were mechanically ventilated for >48 hrs. The incidence of ventilator-associated pneumonia remained significantly lower in period 3 (1999-2001): 23% (period 1, 1995-1996) vs. 15.7% (period 2, 1997-1998) vs. 16.3% (period 3, 1999-2001; p =.002). Late-onset ventilator-associated pneumonia occurred in 86.6% and 94% of cases, respectively, in periods 1 and 3 (p =.02). The decrease of the incidence of early-onset ventilator-associated pneumonia was statistically significant during the 7-yr study period: 13% vs. 9% vs. 5.9% (p =.02). Combined with a higher incidence of late-onset ventilator-associated pneumonia, the incidence of potentially resistant Gram-negative bacilli increased in period 3: 42.2% vs. 34.5% vs. 41.7% (nonsignificant), except for B. cepacia: 11.7% vs. 7.4% vs. 3.7% (p =.005). Nevertheless, the potential antibiotic-resistant Gram-negative bacilli were more sensitive to most of the beta-lactams, especially piperacillin-tazobactam and cefepime.
Rotation of antibiotics could help to avoid ventilator-associated pneumonia. It could greatly improve the susceptibilities of the potentially antibiotic-resistant Gram-negative bacilli responsible for late-onset ventilator-associated pneumonia. This program could be applied in routine with good results 5 yrs after its introduction. Further studies, especially multiple-center trials, are necessary to confirm this result and better define the rotation type and intervals.
评估抗生素轮换方案对呼吸机相关性肺炎发病率以及导致呼吸机相关性肺炎的革兰阴性杆菌敏感性的长期影响。
对导致呼吸机相关性肺炎的微生物进行抗生素敏感性监测的前瞻性方案。
一所大学附属学术性医疗重症监护病房(16张床位)。
2856例机械通气患者。
1996年末引入一项新的抗生素使用方案,该方案涉及在呼吸机相关性肺炎的经验性和治疗性用药中进行抗生素轮换。轮换涉及β-内酰胺类和氨基糖苷类抗生素,轮换间隔为1个月。每月监测抗生素使用情况。不偏爱任何一种特定抗生素。在之前的一项研究中,将引入该方案前的时期(1995 - 1996年)与引入后2年的时期(1997 - 1998年)进行了比较:结果显示呼吸机相关性肺炎发病率降低,潜在耐药革兰阴性杆菌发病率降低,革兰阴性杆菌敏感性增加,尤其是铜绿假单胞菌和洋葱伯克霍尔德菌。1998年后,我们决定继续这一轮换常规操作。通过比较第三个时期(1999 - 2001年)导致呼吸机相关性肺炎的革兰阴性杆菌发病率及其敏感性,研究了该方案的长期影响。可以评估这种策略的长期影响(5年)——2年的方案期(1997 - 1998年)和3年的常规期(1999 - 2001年)。
在7年的研究期间,2856例患者机械通气时间超过48小时。在第3时期(1999 - 2001年),呼吸机相关性肺炎的发病率仍显著较低:23%(第1时期,1995 - 1996年)对比15.7%(第2时期,1997 - 1998年)对比16.3%(第3时期,1999 - 2001年;p = 0.002)。迟发性呼吸机相关性肺炎分别在第1时期和第3时期的病例中占86.6%和94%(p = 0.02)。在7年的研究期间,早发性呼吸机相关性肺炎发病率的降低具有统计学意义:13%对比9%对比5.9%(p = 0.02)。与迟发性呼吸机相关性肺炎较高的发病率相结合,第3时期潜在耐药革兰阴性杆菌的发病率有所增加:42.2%对比34.5%对比41.7%(无显著差异),除了洋葱伯克霍尔德菌:11.7%对比7.4%对比3.7%(p = 0.005)。然而,潜在耐药革兰阴性杆菌对大多数β-内酰胺类抗生素更敏感,尤其是哌拉西林-他唑巴坦和头孢吡肟。
抗生素轮换有助于避免呼吸机相关性肺炎。它可以极大地提高导致迟发性呼吸机相关性肺炎的潜在耐药革兰阴性杆菌的敏感性。该方案在引入5年后可常规应用并取得良好效果。需要进一步研究,尤其是多中心试验,以证实这一结果并更好地确定轮换类型和间隔。