Tigecycline Therapy for Nosocomial Pneumonia due to Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Who Received Inappropriate Initial Antibiotic Treatment: A Retrospective Case Study

Abstract

Background. Nosocomial pneumonia due to carbapenem-resistant Gram-negative bacteria (CRGNB) is a growing concern because treatment options are limited and the mortality rate is high. The effect of tigecycline (TGC) on nosocomial pneumonia due to CRGNB in patients who have received inappropriate initial empiric antibiotic treatment (IIAT) is unclear. Therefore, this study aimed to examine the effect of TGC on nosocomial pneumonia due to CRGNB in critically ill patients who had received IIAT. Methods. A retrospective study was conducted in an adult respiratory intensive care unit. Data were obtained and analyzed for all patients who were treated with TGC ≥ 3 days for microbiologically confirmed nosocomial pneumonia due to CRGNB and had experienced initial antibiotic failure. Clinical and microbiological outcomes were investigated. Results. Thirty-one patients with hospital-acquired pneumonia or ventilator-associated pneumonia were included in the study. The majority of the responsible organisms were carbapenem-resistant Acinetobacter baumannii (67.7%), followed by Klebsiella pneumoniae (16.1%) and Escherichia coli (9.7%). Twenty patients were treated with high-dose TGC therapy (100 mg every 12 h after a 200 mg loading dose), and the others received a standard-dose therapy (50 mg every 12 h after a 100 mg loading dose). The duration of TGC therapy was 14.3 ± 2.8 days. The global clinical cure rate and the microbiological eradication rate were 48.4% and 61.3%, respectively. The overall ICU mortality rate was 45.2%. A higher score on the Acute Physiology and Chronic Health Evaluation II and a longer duration of IIAT were associated with clinical failure. High-dose TGC therapy had a higher clinical success rate [65.0% (13/20) versus 18.2% (2/11), P = 0.023] and a lower ICU mortality rate [30.0% (6/20) versus 72.7% (8/11), P = 0.031] than the standard-dose therapy. Conclusions. TGC, especially a high-dose regimen, might be a justifiable option for critically ill patients with nosocomial pneumonia due to CRGNB who have received IIAT when the options for these patients are limited.

Efficacy and safety of high-dose tigecycline for the treatment of infectious diseases

“…[12] 3 random controlled trial, [12,34,36] among which one was a phase 2 double-blind study, [12] one described the randomization method, [34] while the other without any detail illustration, [36] 3 prospective cohort study [25,28,32] and 11 retrospective cohort study. Studies covered several different countries, including Italy (2 studies [25,26] ), Spain (2 studies [27,39] ), Brazil (1 study [28] ), China (11studies, 3 published in English, [14,31,35] and 8 in Chinese) and one international multicenter. [12]…”

“…Eleven studies [12,14,25–28,31–33,35,39] reporting mortality were included for analysis. All-cause mortality for patients treated with HD tigecycline was significantly lower than LD ( RR 0.67, 95% CI 0.53–0.84, 11 studies, 629 patients) without significant heterogeneity ( P = .30, I 2 = 15%).…”

“…Ten studies [14,26,27,30,31,33–36,38] reported microbiological eradication rate were included for analysis. Microbiological eradication rate of HD regimen was significantly higher than LD ( RR 1.61, 95% CI 1.35–1.93, 10 studies, 580 patients) without significant heterogeneity ( P = .86, I 2 = 0%).…”

A Real-World Study for Polymyxin B in the Treatment of Carbapenems Resistant Gram-Negative Bacilli

“…In infected carbapenem-resistant Acinetobacter baumannii patients without appropriate empirical antimicrobial therapy, the overall mortality rate was 86.1% [21]. The ICU mortality rate was 45.2% in critically ill patients infected with CRGNB who received tigecycline therapy [22], and the in-hospital mortality rate was 62.5% [23]. The 30-day mortality in the treatment of infections due to carbapenem-resistant Enterobacteriaceae was 50% after ceftazidime-avibactam treatment [24].…”

Clinical experience with tigecycline in the treatment of hospital-acquired pneumonia caused by multidrug resistant Acinetobacter baumannii

“…The multivariate analyzes showed that the prolonged tigecycline usage was significantly associated with clinical resolution, whereas higher CURB65 scores, mechanical ventilation and tigecycline resistant to MDRAB have significant association with 30-day mortality, and these results may help to explain previous results. Many studies compared the efficacy of tigecycline in the treatment of MDRAB with other antibiotics, and tigecycline was not recommended as first line treatment for MDRAB because of the higher mortality and lower microbiological success, especially for bacteremia [6–8, 20]. However, further analysis showed that the increased mortality rate of tigecycline is significant higher only among those with MIC>2 mg/L, but not for those with MIC≤2 mg/L.…”