Can Enterobacter cloacae be treated with Aztreonam (aztreonam)?

From the Guidelines

Aztreonam should not be used alone to treat Enterobacter cloacae infections, but it can be used in combination with ceftazidime/avibactam as a preferred treatment option for metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) infections, including those caused by Enterobacter cloacae, as recommended by a recent guideline endorsed by the Italian Society of Infection and Tropical Diseases 1.

When considering treatment options for Enterobacter cloacae infections, it's essential to note that aztreonam has in vitro activity against this organism, but its use as a monotherapy is limited due to the potential for resistance development 1. The combination of ceftazidime/avibactam plus aztreonam has shown in vitro synergy and has been associated with improved clinical outcomes, including lower 30-day mortality rates, in patients with MBL-producing CRE infections 1.

Key considerations for treating Enterobacter cloacae infections with aztreonam include:

• Aztreonam's mechanism of action as a monobactam antibiotic that inhibits cell wall synthesis in gram-negative bacteria
• The potential for Enterobacter cloacae to develop resistance to aztreonam through inducible AmpC beta-lactamase production
• The importance of susceptibility testing before initiating therapy and closely monitoring clinical response
• The preference for combination therapies, such as ceftazidime/avibactam plus aztreonam, for MBL-producing CRE infections, including those caused by Enterobacter cloacae 1

In summary, while aztreonam can be used to treat Enterobacter cloacae infections, its use should be guided by susceptibility testing and clinical response, and combination therapies should be considered for serious or resistant infections, as supported by recent guidelines and studies 1.

From the FDA Drug Label

AZACTAM is indicated for the treatment of the following infections caused by susceptible Gram-negative microorganisms: ... Intra-abdominal Infections, including peritonitis caused by ... Enterobacter species including E. cloacae*, AZACTAM is effective against most of the commonly encountered Gram-negative aerobic pathogens Aztreonam has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections ... Aerobic Gram-negative microorganisms: ... Enterobacter species

Treatment of Enterobacter cloacae with Aztreonam is possible.

• The drug label indicates that Aztreonam is effective against Enterobacter species, including E. cloacae.
• Aztreonam has been shown to be active against most strains of Enterobacter species, both in vitro and in clinical infections 2, 2.
• Key points:
  • Aztreonam is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis.
  • Aztreonam has activity in the presence of some beta-lactamases of Gram-negative bacteria.

From the Research

Treatment of Enterobacter cloacae with Aztreonam

• Aztreonam is a monobactam antibiotic that is active against Gram-negative aerobic bacteria, including Enterobacteriaceae, but its effectiveness against Enterobacter species is limited 3.
• According to a study published in 1986, aztreonam is inhibitory at low concentrations against Enterobacteriaceae, except Enterobacter species 3.
• Another study published in 1990 found that aztreonam was more active than third-generation cephalosporins and comparable with mezlocillin against Enterobacter spp. 4.
• However, a more recent study published in 2022 found that the combination of aztreonam with avibactam (ATM-AVI) demonstrated potent antimicrobial activity against Enterobacter cloacae complex, with 99.9% of isolates inhibited at MIC ≤8 mg/L 5.
• The study also found that ATM-AVI was highly active against multidrug-resistant, extended-spectrum β-lactamase producing, and carbapenem-resistant isolates, including those producing metallo-β-lactamases (MBLs) 5.

Limitations of Aztreonam

• Aztreonam is inactive against Gram-positive aerobic bacteria and anaerobes, including Bacteroides fragilis 3.
• Aztreonam must be administered intravenously or intramuscularly, as its absolute bioavailability is very low after oral administration 3.
• The elimination half-life of aztreonam is less than 2 hours, requiring 6- or 8-hourly administration for moderately severe or severe infections 3.

Clinical Uses of Aztreonam

• Aztreonam can be used to treat urinary tract, lower respiratory tract, and intraabdominal infections, as well as septicemia, endometritis, pelvic cellulitis, and skin and skin structure infections due to aerobic Gram-negative organisms 6.
• However, combination therapy is recommended for mixed infections or those of unknown etiology to ensure coverage of Gram-positive and anaerobic bacteria 6.