What is the treatment for Enterobacterales (Enterobacteriales) infection?

From the Guidelines

Treatment of Enterobacterales infections should be guided by the specific organism, infection site, and antibiotic susceptibility patterns, with a strong recommendation for the use of ceftazidime/avibactam or meropenem/vaborbactam as first-line treatment options for carbapenem-resistant Enterobacterales (CRE) infections, as supported by recent guidelines and studies 1. The choice of antibiotic therapy for Enterobacterales infections depends on several factors, including the severity of the infection, the site of infection, and the susceptibility patterns of the organism.

• For uncomplicated urinary tract infections, oral options such as trimethoprim-sulfamethoxazole, nitrofurantoin, or fluoroquinolones like ciprofloxacin may be considered.
• For more severe infections, such as bloodstream infections or pneumonia, intravenous antibiotics like ceftazidime/avibactam or meropenem/vaborbactam may be necessary.
• The treatment duration varies by infection type, ranging from 3-5 days for uncomplicated UTIs to 7-14 days for bacteremia or pneumonia.
• Combination therapy may be necessary for severe infections, often adding an aminoglycoside like gentamicin or amikacin.
• Source control through drainage of abscesses or removal of infected devices is crucial when applicable.
• Antibiotic resistance is increasingly common in Enterobacterales, particularly extended-spectrum beta-lactamase (ESBL) producers and carbapenem-resistant organisms, so treatment should be adjusted based on culture results and local resistance patterns 1. In the case of metallo-β-lactamase (MBL)-producing CRE, the combination of ceftazidime/avibactam plus aztreonam is recommended as the first-line treatment option, with cefiderocol as an alternative option 1.
• The use of ceftazidime/avibactam plus aztreonam has shown in vitro synergy and improved clinical outcomes in patients with MBL-producing CRE infections.
• Cefiderocol may also be considered, particularly for infections caused by MBL-producing CRE, with recent studies showing promising results in terms of clinical cure and microbiological eradication 1.

From the FDA Drug Label

AVYCAZ (ceftazidime and avibactam) in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa. AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa. AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae. PIPRACIL is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the conditions listed below: Septicemia including bacteremia caused by E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., P. mirabilis, S. pneumoniae, enterococci, P. aeruginosa, Bacteroides spp., or anaerobic cocci. Lower RespiratoryTract Infections caused by E. coli, Klebsiella spp., Enterobacter spp., P. aeruginosa, Serratia spp., H. influenzae, Bacteroides spp., or anaerobic cocci. Skin and Skin Structure Infections caused by E. coli, Klebsiella spp., Serratia spp., Acinetobacter spp., Enterobacter spp., P. aeruginosa, Morganella morganii, Providencia rettgeri, Proteus vulgaris, P. mirabilis, Bacteroides spp., including B. fragilis, anaerobic cocci, or enterococci.

The treatment for Enterobacterales infection includes:

• AVYCAZ (ceftazidime and avibactam) for complicated intra-abdominal infections, complicated urinary tract infections, and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible gram-negative microorganisms, including Enterobacter cloacae and Klebsiella pneumoniae 2.
• PIPRACIL (piperacillin) for septicemia, lower respiratory tract infections, and skin and skin structure infections caused by susceptible strains of Enterobacter spp., Klebsiella spp., and Escherichia coli 3. Key points:
• The choice of treatment depends on the specific type of infection, the severity of the infection, and the susceptibility of the microorganism to the antibiotic.
• It is essential to use antibiotics judiciously and only when necessary to reduce the development of drug-resistant bacteria.

From the Research

Treatment Options for Enterobacterales Infections

The treatment for Enterobacterales infections depends on the type of infection and the resistance pattern of the bacteria.

• For carbapenem-resistant Enterobacteriaceae (CRE) infections, treatment options are limited and include the use of older agents such as polymyxins, fosfomycin, and aminoglycosides 4.
• For extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales infections, carbapenems are considered the first-line therapy, but carbapenem-sparing strategies such as ceftolozane-tazobactam and ceftazidime-avibactam are also effective 5.
• For AmpC-producing Enterobacterales infections, cefepime (FEP) has been shown to be a clinically useful carbapenem-sparing alternative 6.
• For metallo-beta-lactamases-producing (MBL) Enterobacterales infections, combination therapy with ceftazidime/avibactam and aztreonam or cefiderocol is recommended 7.
• For nonbacteremic urinary tract infections (UTIs) due to ESBL-producing Enterobacterales, piperacillin-tazobactam (PTZ) may be an effective alternative to carbapenems 8.

Considerations for Treatment

When treating Enterobacterales infections, it is essential to consider the following:

• The resistance pattern of the bacteria
• The severity of the infection
• The patient's underlying health conditions
• The potential for toxicity and side effects of the treatment
• The need for combination therapy or carbapenem-sparing strategies
• The importance of individualized treatment plans and close collaboration between healthcare professionals 4, 5, 6, 7, 8.