Urosepsis Treatment with Ceftazidime-Avibactam and Aztreonam

Introduction to Treatment Options

The European Association of Urology recommends ceftazidime-avibactam as an appropriate treatment option for complicated urinary tract infections (UTIs), which can progress to urosepsis, particularly for carbapenem-resistant Enterobacterales (CRE) 1, 2, 3

Ceftazidime-avibactam is recommended for complicated UTIs caused by CRE at a dosage of 2.5 g IV q8h, and is effective against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and OXA-48-producing Enterobacterales 1
The European Association of Urology guidelines support the use of ceftazidime-avibactam for complicated UTIs that can lead to urosepsis 2, 3

Aztreonam is uniquely active against metallo-beta-lactamase (MBL)-producing CRE, which are resistant to ceftazidime-avibactam, and can be used in combination with ceftazidime-avibactam for MBL-producing pathogens 4

For patients with urosepsis, early antimicrobial therapy must be initiated immediately after microbiological sampling to improve outcomes, with ceftazidime-avibactam as a first-line option for CRE and aztreonam for MBL-producing pathogens 5
The treatment algorithm for urosepsis involves initial empiric therapy with ceftazidime-avibactam, with consideration of adding aztreonam for MBL-producing organisms based on culture results, and de-escalation to narrower spectrum antibiotics for susceptible organisms 1, 5, 4
Source control measures, including alleviating urinary tract obstruction and draining significant abscesses, and replacing or removing indwelling catheters, are crucial in the management of urosepsis 5

The duration of therapy for urosepsis generally ranges from 7-14 days, depending on the severity of the infection and the patient's response, with longer courses needed if prostatitis cannot be excluded in men 3

The Infectious Diseases Society of America recommends ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacterales (CRE) infections, including bloodstream infections, complicated urinary tract infections, and complicated intra-abdominal infections, with a dosage of 2.5 g IV q8h 6, 7, 8
Ceftazidime-avibactam is effective against difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections, with a recommended dosage of 2.5 g IV q8h 9

Ceftazidime-avibactam is active against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms, OXA-48-producing Enterobacterales, with a strength of evidence based on in vitro studies 10

The Centers for Disease Control and Prevention notes that resistance to ceftazidime-avibactam in KPC-producing organisms has been reported, particularly with prior ceftazidime-avibactam exposure, highlighting the need for careful use and monitoring 7, 10
Combination therapy with ceftazidime-avibactam plus a carbapenem or colistin may be considered when treating KPC-3 producers due to potential resistance development, based on expert opinion 7