Rottier Wouter C, Deelen J W Timotëus, Caruana Giorgia, Buiting Anton G M, Dorigo-Zetsma J Wendelien, Kluytmans Jan A J W, van der Linden Paul D, Thijsen Steven F T, Vlaminckx Bart J M, Weersink Annemarie J L, Ammerlaan Heidi S M, Bonten Marc J M
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Clin Microbiol Infect. 2020 Jul 19. doi: 10.1016/j.cmi.2020.07.014.
Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands.
In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection.
We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66-3.09) and 1.32 (1.06-1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48-2.41).
In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections.
革兰氏阴性菌的抗生素耐药性与死亡率增加有关。这在国际研究中主要是针对耐第三代头孢菌素（3GC-R）的肠杆菌科菌血症得到证实的。然而，荷兰特定的耐药负担以及由各类革兰氏阴性菌感染造成的负担尚未得到量化。因此，我们调查了荷兰革兰氏阴性菌感染中抗生素耐药性导致的可归因死亡率。
在八家医院中，确定了2013年至2016年间革兰氏阴性菌感染的样本，并将其分为耐药感染队列和敏感感染队列。两个队列均按照医院、感染发作时的住院时长和年龄与未感染的对照患者进行1:1匹配。在这种平行匹配队列设置中，比较了感染患者和未感染患者的30天死亡率。然后通过划分革兰氏阴性菌感染导致死亡的两个单独风险比（RRs）来评估耐药性的影响。
我们确定了1954例革兰氏阴性菌感染，其中1190例（61%）涉及大肠杆菌，210例（11%）铜绿假单胞菌，758例（39%）菌血症。耐药革兰氏阴性菌导致243例感染（12%；189例（78%）耐3GC-R的肠杆菌科细菌，9例（4%）多重耐药铜绿假单胞菌，无产碳青霉烯酶的肠杆菌科细菌）。随后，我们匹配了1941例未感染的对照。调整后，比较感染组和对照组死亡率的RRs点估计值在耐药感染和敏感感染情况下同样高于1（分别为1.42（95%置信区间0.66 - 3.09）和1.32（1.06 - 1.65））。通过划分这些值，反映耐药性可归因死亡率的RR计算为1.08（0.48 - 2.41）。
在荷兰，抗生素耐药性并未增加革兰氏阴性菌感染的30天死亡率。
