Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins

Abstract

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 μg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Successful Engraftment of HLA-matched Peripheral Hematopoietic-stem-cell Transplantation for Severe Aplastic Anemia With Multidrug-resistant Bacterial and Fungal Infections

“…Ceftazidimeavibactam (CAZ-AVI) is a novel synthetic β-lactamase inhibitor combination for a range of MDR Gramnegative infection [15,16], which was approved by the FDA in 2017. CAZ-AVI has been successfully used in patients with limited treatment options for complicated intra-abdominal infections and hospitalacquired, ventilator-associated pneumonia caused by CRE and other multidrug Gram-negative bacteria [17][18][19]. In the present study, the patient showed gradual improvement after treatment with CAZ-AVI and fosfomycin.…”

Impact of the COVID-19 pandemic on the incidence of multidrug-resistant bacterial infections in an acute care hospital in Brazil

“… 24 , 25 , 26 . The need to stay ahead of infection in the critically ill pushes clinicians towards a greater use of broad-spectrum antimicrobials in mechanically ventilated patients due to the difficulty in distinguishing the inflammatory phase of COVID-19 with the appearance of secondary infection [ 8 , 16 ]. Future studies are warranted to evaluate the changes in incidence of MDR infections during COVID-19 in Brazil with changes in antibiotic prescribing patterns.…”

An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2–Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting

“…In contrast, ST16 KP has rarely been described harboring bla KPC , except for 2 isolates reported in Rio de Janeiro in 2008 and 2009 ( bla KPC-2 ) and 1 isolate in Israel. More recently, KPC-2–producing K. pneumoniae ST16 was detected in another teaching hospital also located in São Paulo [ 32 ]. This study thus depicts the largest outbreak caused by KPC-ST16 [ 16 , 17 , 33 ], which is a poorly characterized clone, in contrast to the successful ST11, ST258, ST307, or ST15 clones (also found in this study) [ 9 , 12 , 34–37 ].…”